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  • 251.
    Hosseinzadeh, Ava
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Novel Insight into Neutrophil Immune Responses by Dry Mass Determination of Candida albicans Morphotypes2013Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 10, artikkel-id e77993Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The common fungal pathogen Candida albicans has the ability to grow as a yeast or as a hypha and can alternate between these morphotypes. The overall biomass of both morphotypes increases with growth. However, only yeasts, but not hyphae, exist as discrete cellular entities. Multiplicity of infection (MOI) is a useful parameter to determine the initial inoculum of yeasts for in vitro infection assays. Since the amount of hyphae is difficult to quantify, comparable starting conditions in such assays cannot be determined accurately for yeasts and hyphae using MOI. To circumvent this problem, we have established a set of correlation coefficients to convert fungal metabolic activity and optical density to dry mass. Using these correlations, we were able to accurately compare ROS production and IL-8 release by polymorphonuclear neutrophils upon infection with equal dry mass amounts of yeast and hyphal morphotypes. Neutrophil responses depended on the initial form of infection, irrespective of C. albicans wild-type yeasts transforming to hyphal growth during the assay. Infection with a high mass of live C. albicans yeasts resulted in lower neutrophil ROS and this decrease stems from efficient ROS detoxification by C. albicans without directly affecting the phagocyte ROS machinery. Moreover, we show that dead C. albicans induces significantly less ROS and IL-8 release than live fungi, but thimerosal-killed C. albicans were still able to detoxify neutrophil ROS. Thus, the dry mass approach presented in this study reveals neutrophil responses to different amounts and morphotypes of C. albicans and serves as a template for studies that aim to identify morphotype-specific responses in a variety of immune cells.

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  • 252. Howell, Matthew
    et al.
    Aliashkevich, Alena
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Salisbury, Anne K.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Bowman, Grant R.
    Brown, Pamela J. B.
    Absence of the Polar Organizing Protein PopZ Results in Reduced and Asymmetric Cell Division in Agrobacterium tumefaciens2017Inngår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 199, nr 17, artikkel-id e00101-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Agrobacterium tumefaciens is a rod-shaped bacterium that grows by polar insertion of new peptidoglycan during cell elongation. As the cell cycle progresses, peptidoglycan synthesis at the pole ceases prior to insertion of new peptidoglycan at midcell to enable cell division. The A. tumefaciens homolog of the Caulobacter crescentus polar organelle development protein PopZ has been identified as a growth pole marker and a candidate polar growth-promoting factor. Here, we characterize the function of PopZ in cell growth and division of A. tumefaciens. Consistent with previous observations, we observe that PopZ localizes specifically to the growth pole in wild-type cells. Despite the striking localization pattern of PopZ, we find the absence of the protein does not impair polar elongation or cause major changes in the peptidoglycan composition. Instead, we observe an atypical cell length distribution, including minicells, elongated cells, and cells with ectopic poles. Most minicells lack DNA, suggesting a defect in chromosome segregation. Furthermore, the canonical cell division proteins FtsZ and FtsA are misplaced, leading to asymmetric sites of cell constriction. Together, these data suggest that PopZ plays an important role in the regulation of chromosome segregation and cell division.

    IMPORTANCE A. tumefaciens is a bacterial plant pathogen and a natural genetic engineer. However, very little is known about the spatial and temporal regulation of cell wall biogenesis that leads to polar growth in this bacterium. Understanding the molecular basis of A. tumefaciens growth may allow for the development of innovations to prevent disease or to promote growth during biotechnology applications. Finally, since many closely related plant and animal pathogens exhibit polar growth, discoveries in A. tumefaciens may be broadly applicable for devising antimicrobial strategies.

  • 253. Howell, Matthew
    et al.
    Aliashkevich, Alena
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sundararajan, Kousik
    Daniel, Jeremy J.
    Lariviere, Patrick J.
    Goley, Erin D.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Brown, Pamela J. B.
    Agrobacterium tumefaciens divisome proteins regulate the transition from polar growth to cell division2019Inngår i: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 111, nr 4, s. 1074-1092Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mechanisms that restrict peptidoglycan biosynthesis to the pole during elongation and re-direct peptidoglycan biosynthesis to mid-cell during cell division in polar-growing Alphaproteobacteria are largely unknown. Here, we explore the role of early division proteins of Agrobacterium tumefaciens including three FtsZ homologs, FtsA and FtsW in the transition from polar growth to mid-cell growth and ultimately cell division. Although two of the three FtsZ homologs localize to mid-cell, exhibit GTPase activity and form co-polymers, only one, FtsZ(AT), is required for cell division. We find that FtsZ(AT) is required not only for constriction and cell separation, but also for initiation of peptidoglycan synthesis at mid-cell and cessation of polar peptidoglycan biosynthesis. Depletion of FtsZ(AT) in A. tumefaciens causes a striking phenotype: cells are extensively branched and accumulate growth active poles through tip splitting events. When cell division is blocked at a later stage by depletion of FtsA or FtsW, polar growth is terminated and ectopic growth poles emerge from mid-cell. Overall, this work suggests that A. tumefaciens FtsZ makes distinct contributions to the regulation of polar growth and cell division.

  • 254.
    Huang, Shenghua
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hainzl, Tobias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Grundström, Christin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Forsman, Cecilia
    Orphan Biovitrum AB, Umeå, Sweden.
    Samuelsson, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Sauer-Eriksson, A Elisabeth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Structural studies of β-Carbonic Anhydrase from the Green Alga Coccomyxa: Inhibitor complexes with Anions and Acetazolamide2011Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 6, nr 12, s. e28458-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The β-class carbonic anhydrases (β-CAs) are widely distributed among lower eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the β-enzymes catalyze an important physiological reaction, namely the interconversion between carbon dioxide and bicarbonate. In plants the enzyme plays an important role in carbon fixation and metabolism. To further explore the structure-function relationship of β-CA, we have determined the crystal structures of the photoautotroph unicellular green alga Coccomyxa β-CA in complex with five different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate ions. The tetrameric Coccomyxa β-CA structure is similar to other β-CAs but it has a 15 amino acid extension in the C-terminal end, which stabilizes the tetramer by strengthening the interface. Four of the five inhibitors bind in a manner similar to what is found in complexes with α-type CAs. Iodide ions, however, make contact to the zinc ion via a zinc-bound water molecule or hydroxide ion - a type of binding mode not previously observed in any CA. Binding of inhibitors to Coccomyxa β-CA is mediated by side-chain movements of the conserved residue Tyr-88, extending the width of the active site cavity with 1.5-1.8 Å. Structural analysis and comparisons with other α- and β-class members suggest a catalytic mechanism in which the movements of Tyr-88 are important for the CO(2)-HCO(3) (-) interconversion, whereas a structurally conserved water molecule that bridges residues Tyr-88 and Gln-38, seems important for proton transfer, linking water molecules from the zinc-bound water to His-92 and buffer molecules.

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  • 255. Humphreys, Daniel
    et al.
    ElGhazaly, Mohamed
    Frisan, Teresa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Senescence and Host-Pathogen Interactions2020Inngår i: Cells, E-ISSN 2073-4409, Vol. 9, nr 7, artikkel-id 1747Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host-pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease.

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  • 256. Hurwitz, Julia L.
    et al.
    Jones, Bart G.
    Charpentier, Emmanuelle
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Max Planck Institute for Infection Biology, Berlin, Germany; Humboldt University, Berlin, Germany.
    Woodland, David L.
    Hypothesis: RNA and DNA Viral Sequence Integration into the Mammalian Host Genome Supports Long-Term B Cell and T Cell Adaptive Immunity2017Inngår i: Viral immunology, ISSN 0882-8245, E-ISSN 1557-8976, Vol. 30, nr 9, s. 628-632Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e.g., to support host cell development or to silence foreign invaders). Here we propose that, comparable with the clustered regularly interspaced short palindromic repeats that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory. We hypothesize that host cells express viral peptides from open reading frames in integrated sequences to boost adaptive B cell and T cell responses long after replicating viruses are cleared. In support of this hypothesis, we examine previous literature describing (1) viruses that infect acutely (e.g., vaccinia viruses and orthomyxoviruses) followed by unexplained, long-term persistence of viral nucleotide sequences, viral peptides, and virus-specific adaptive immunity, (2) the high frequency of endogenous viral genetic elements found in animal genomes, and (3) mechanisms with which animal host machinery supports foreign sequence integration.

  • 257.
    Härtlova, Anetta
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Erttmann, Saskia F.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Raffi, Faizal A. M.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Schmalz, Anja M.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Resch, Ulrike
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Anugula, Sharath
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lienenklaus, Stefan
    Nilsson, Lisa M.
    Kroeger, Andrea
    Nilsson, Jonas A.
    Ek, Torben
    Weiss, Siegfried
    Gekara, Nelson O.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity2015Inngår i: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 42, nr 2, s. 332-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dysfunction in Ataxia-telangiectasia mutated (ATM), a central component of the DNA repair machinery, results in Ataxia Telangiectasia (AT), a cancer-prone disease with a variety of inflammatory manifestations. By analyzing AT patient samples and Atm(-/-) mice, we found that unrepaired DNA lesions induce type I interferons (IFNs), resulting in enhanced anti-viral and anti-bacterial responses in Atm(-/-) mice. Priming of the type I interferon system by DNA damage involved release of DNA into the cytoplasm where it activated the cytosolic DNA sensing STING-mediated pathway, which in turn enhanced responses to innate stimuli by activating the expression of Toll-like receptors, RIG-I-like receptors, cytoplasmic DNA sensors, and their downstream signaling partners. This study provides a potential explanation for the inflammatory phenotype of AT patients and establishes damaged DNA as a cell intrinsic danger signal that primes the innate immune system for a rapid and amplified response to microbial and environmental threats.

  • 258.
    Ignatov, Dmitriy
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    RNA-mediated signal perception in pathogenic bacteria2017Inngår i: Wiley Interdisciplinary Reviews-RNA, ISSN 1757-7004, Vol. 8, nr 6, artikkel-id e1429Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Bacterial pathogens encounter several different environments during an infection, many of them possibly being detrimental. In order to sense its surroundings and adjust the gene expression accordingly, different regulatory schemes are undertaken. With these, the bacterium appropriately can differentiate between various environmental cues to express the correct virulence factor at the appropriate time and place. An attractive regulator device is RNA, which has an outstanding ability to alter its structure in response to external stimuli, such as metabolite concentration or alterations in temperature, to control its downstream gene expression. This review will describe the function of riboswitches and thermometers, with a particular emphasis on regulatory RNAs being important for bacterial pathogenicity.

  • 259.
    Ignatov, Dmitriy
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Vaitkevicius, Karolis
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Durand, Sylvain
    Cahoon, Laty
    Sandberg, Stefanie
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Liu, Xijia
    Kallipolitis, Birgitte H.
    Ryden, Patrik
    Freitag, Nancy
    Condon, Ciaran
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    An mRNA-mRNA Interaction Couples Expression of a Virulence Factor and Its Chaperone in Listeria monocytogenes2020Inngår i: Cell Reports, E-ISSN 2211-1247, Vol. 30, nr 12, s. 4027-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bacterial pathogens often employ RNA regulatory elements located in the 5' untranslated regions (UTRs) to control gene expression. Using a comparative structural analysis, we examine the structure of 5' UTRs at a global scale in the pathogenic bacterium Listeria monocytogenes under different conditions. In addition to discovering an RNA thermoswitch and detecting simultaneous interaction of ribosomes and small RNAs with mRNA, we identify structural changes in the 5' UTR of an mRNA encoding the post-translocation chaperone PrsA2 during infection conditions. We demonstrate that the 5' UTR of the prsA2 mRNA base pairs with the 3' UTR of the full-length hly mRNA encoding listeriolysin O, thus preventing RNase J1-mediated degradation of the prsA2 transcript. Mutants lacking the hly-prsA2 interaction exhibit reduced virulence properties. This work highlights an additional level of RNA regulation, where the mRNA encoding a chaperone is stabilized by the mRNA encoding its substrate.

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  • 260.
    Ignatov, Dmitriy
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Vaitkevicius, Karolis
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Generation of Sequencing Libraries for Structural Analysis of Bacterial 5′ UTRs2020Inngår i: STAR Protocols, E-ISSN 2666-1667, Vol. 1, nr 2, artikkel-id 100046Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The structure of 5′ untranslated regions (5′ UTRs) of bacterial mRNAs often determines the fate of the transcripts. Using a dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) approach, we developed a protocol to generate sequence libraries to determine the base-pairing status of adenines and cytosines in the 5′ UTRs of bacterial mRNAs. Our method increases the sequencing depth of the 5′ UTRs and allows detection of changes in their structures by sequencing libraries of moderate sizes. For complete details on the use and execution of this protocol, please refer to Ignatov et al. (2020).

    Fulltekst (pdf)
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  • 261.
    Irazoki, Oihane
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    ter Beek, Josy
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Alvarez, Laura
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Mateus, André
    Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
    Colin, Remy
    Max Planck Institute for Terrestrial Microbiology, and Center for Synthetic Microbiology (SYNMIKRO), Marburg, Germany.
    Typas, Athanasios
    Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
    Savitski, Mikhail M.
    Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
    Sourjik, Victor
    Max Planck Institute for Terrestrial Microbiology, and Center for Synthetic Microbiology (SYNMIKRO), Marburg, Germany.
    Berntsson, Ronnie P.-A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    D-amino acids signal a stress-dependent run-away response in Vibrio cholerae2023Inngår i: Nature Microbiology, E-ISSN 2058-5276, Vol. 8, nr 8, s. 1549-1560Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To explore favourable niches while avoiding threats, many bacteria use a chemotaxis navigation system. Despite decades of studies on chemotaxis, most signals and sensory proteins are still unknown. Many bacterial species release d-amino acids to the environment; however, their function remains largely unrecognized. Here we reveal that d-arginine and d-lysine are chemotactic repellent signals for the cholera pathogen Vibrio cholerae. These d-amino acids are sensed by a single chemoreceptor MCPDRK co-transcribed with the racemase enzyme that synthesizes them under the control of the stress-response sigma factor RpoS. Structural characterization of this chemoreceptor bound to either d-arginine or d-lysine allowed us to pinpoint the residues defining its specificity. Interestingly, the specificity for these d-amino acids appears to be restricted to those MCPDRK orthologues transcriptionally linked to the racemase. Our results suggest that d-amino acids can shape the biodiversity and structure of complex microbial communities under adverse conditions.

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  • 262.
    Ishikawa, Takahiko
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sabharwal, Dharmesh
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Bröms, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Milton, Debra L
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Pathoadaptive conditional regulation of the type VI secretion system in Vibrio cholerae O1 strains2012Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, nr 2, s. 575-584Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The most recently discovered secretion pathway in gram-negative bacteria, the type VI secretion system (T6SS), is present in many species and is considered important for the survival of non-O1 non-O139 Vibrio cholerae in aquatic environments. Until now, it was not known whether there is a functionally active T6SS in wild-type V. cholerae O1 strains, the cause of cholera disease in humans. Here, we demonstrate the presence of a functionally active T6SS in wild-type V. cholerae O1 strains, as evidenced by the secretion of the T6SS substrate Hcp, which required several gene products encoded within the putative vas gene cluster. Our analyses showed that the T6SS of wild-type V. cholerae O1 strain A1552 was functionally activated when the bacteria were grown under high-osmolarity conditions. The T6SS was also active when the bacteria were grown under low temperature (23°C), suggesting that the system may be important for the survival of the bacterium in the environment. A test of the interbacterial virulence of V. cholerae strain A1552 against an Escherichia coli K-12 strain showed that it was strongly enhanced under high osmolarity and that it depended on the hcp genes. Interestingly, we found that the newly recognized osmoregulatory protein OscR plays a role in the regulation of T6SS gene expression and secretion of Hcp from V. cholerae O1 strains.

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  • 263.
    Jafari, Shadi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Henriksson, Johan
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Yan, Hua
    Department of Biology, University of Florida, FL, Gainesville, United States.
    Alenius, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila2021Inngår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 19, nr 4, artikkel-id e3001101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here, we reveal that the regulation of Drosophila odorant receptor (OR) expression during the pupal stage is permissive and imprecise. We found that directly after hatching an OR feedback mechanism both directs and refines OR expression. We demonstrate that, as in mice, dLsd1 and Su(var)3-9 balance heterochromatin formation to direct OR expression. We show that the expressed OR induces dLsd1 and Su(var)3-9 expression, linking OR level and possibly function to OR expression. OR expression refinement shows a restricted duration, suggesting that a gene regulatory critical period brings olfactory sensory neuron differentiation to an end. Consistent with a change in differentiation, stress during the critical period represses dLsd1 and Su(var)3-9 expression and makes the early permissive OR expression permanent. This induced permissive gene regulatory state makes OR expression resilient to stress later in life. Hence, during a critical period OR feedback, similar to in mouse OR selection, defines adult OR expression in Drosophila.

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  • 264.
    Jaiman, Deepika
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nagampalli, Raghavendra
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Persson, Karina
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    A comparative analysis of lipoprotein transport proteins: LolA and LolB from Vibrio cholerae and LolA from Porphyromonas gingivalis2023Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikkel-id 6605Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Gram-negative bacteria, N-terminal lipidation is a signal for protein trafficking from the inner membrane (IM) to the outer membrane (OM). The IM complex LolCDE extracts lipoproteins from the membrane and moves them to the chaperone LolA. The LolA-lipoprotein complex crosses the periplasm after which the lipoprotein is anchored to the OM. In γ-proteobacteria anchoring is assisted by the receptor LolB, while a corresponding protein has not been identified in other phyla. In light of the low sequence similarity between Lol-systems from different phyla and that they may use different Lol components, it is crucial to compare representative proteins from several species. Here we present a structure-function study of LolA and LolB from two phyla: LolA from Porphyromonas gingivalis (phylum bacteroidota), and LolA and LolB from Vibrio cholerae (phylum proteobacteria). Despite large sequence differences, the LolA structures are very similar, hence structure and function have been conserved throughout evolution. However, an Arg-Pro motif crucial for function in γ-proteobacteria has no counterpart in bacteroidota. We also show that LolA from both phyla bind the antibiotic polymyxin B whereas LolB does not. Collectively, these studies will facilitate the development of antibiotics as they provide awareness of both differences and similarities across phyla.

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  • 265.
    Jespersen, Nathan
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Ehrenbolger, Kai
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Winiger, Rahel
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Svedberg, Dennis
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Vossbrinck, Charles R.
    Department of Environmental Science, Connecticut Agricultural Experiment Station, CT, New Haven, United States.
    Barandun, Jonas
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores2022Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 13, nr 1, artikkel-id 6962Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proteasomes play an essential role in the life cycle of intracellular pathogens with extracellular stages by ensuring proteostasis in environments with limited resources. In microsporidia, divergent parasites with extraordinarily streamlined genomes, the proteasome complexity and structure are unknown, which limits our understanding of how these unique pathogens adapt and compact essential eukaryotic complexes. We present cryo-electron microscopy structures of the microsporidian 20S and 26S proteasome isolated from dormant or germinated Vairimorpha necatrix spores. The discovery of PI31-like peptides, known to inhibit proteasome activity, bound simultaneously to all six active sites within the central cavity of the dormant spore proteasome, suggests reduced activity in the environmental stage. In contrast, the absence of the PI31-like peptides and the existence of 26S particles post-germination in the presence of ATP indicates that proteasomes are reactivated in nutrient-rich conditions. Structural and phylogenetic analyses reveal that microsporidian proteasomes have undergone extensive reductive evolution, lost at least two regulatory proteins, and compacted nearly every subunit. The highly derived structure of the microsporidian proteasome, and the minimized version of PI31 presented here, reinforce the feasibility of the development of specific inhibitors and provide insight into the unique evolution and biology of these medically and economically important pathogens.

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  • 266.
    Jespersen, Nathan
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Monrroy, Leonardo
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Barandun, Jonas
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Impact of genome reduction in microsporidia2022Inngår i: Microsporidia: current advances in biology / [ed] Louis M. Weiss; Aaron W. Reinke, Cham: Springer, 2022, 1, Vol. 114, s. 1-42Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Microsporidia represent an evolutionary outlier in the tree of life and occupy the extreme edge of the eukaryotic domain with some of their biological features. Many of these unicellular fungi-like organisms have reduced their genomic content to potentially the lowest limit. With some of the most compacted eukaryotic genomes, microsporidia are excellent model organisms to study reductive evolution and its functional consequences. While the growing number of sequenced microsporidian genomes have elucidated genome composition and organization, a recent increase in complementary post-genomic studies has started to shed light on the impacts of genome reduction in these unique pathogens. This chapter will discuss the biological framework enabling genome minimization and will use one of the most ancient and essential macromolecular complexes, the ribosome, to illustrate the effects of extreme genome reduction on a structural, molecular, and cellular level. We outline how reductive evolution in microsporidia has shaped DNA organization, the composition and function of the ribosome, and the complexity of the ribosome biogenesis process. Studying compacted mechanisms, processes, or macromolecular machines in microsporidia illuminates their unique lifestyle and provides valuable insights for comparative eukaryotic structural biology.

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  • 267.
    Jia, Xiaotong
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Knyazeva, Anastasia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Zhang, Yu
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Castro-Gonzalez, Sergio
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Nakamura, Shuhei
    Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.
    Carlson, Lars-Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Yoshimori, Tamotsu
    Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.
    Corkery, Dale
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Wu, Yao-Wen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy2022Inngår i: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 221, nr 12, artikkel-id e202206040Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pore-forming toxins (PFTs) are important virulence factors produced by many pathogenic bacteria. Here, we show that the Vibrio cholerae toxin MakA is a novel cholesterol-binding PFT that induces non-canonical autophagy in a pH-dependent manner. MakA specifically binds to cholesterol on the membrane at pH < 7. Cholesterol-binding leads to oligomerization of MakA on the membrane and pore formation at pH 5.5. Unlike other cholesterol-dependent cytolysins (CDCs) which bind cholesterol through a conserved cholesterol-binding motif (Thr-Leu pair), MakA contains an Ile-Ile pair that is essential for MakA-cholesterol interaction. Following internalization, endosomal acidification triggers MakA pore-assembly followed by ESCRT-mediated membrane repair and V-ATPase-dependent unconventional LC3 lipidation on the damaged endolysosomal membranes. These findings characterize a new cholesterol-binding toxin that forms pores in a pH-dependent manner and reveals the molecular mechanism of host autophagy manipulation.

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  • 268.
    Jiang, Hui
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Panda, Swarupa
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Gekara, Nelson O.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Comet and micronucleus assays for analyzing DNA damage and genome integrity2019Inngår i: DNA SENSORS AND INFLAMMASOMES / [ed] Sohn, J, ELSEVIER ACADEMIC PRESS INC , 2019, s. 299-307Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Detection of DNA damage in cells is fundamental for the study of DNA repair and genome-instability associated processes including carcinogenesis. Many studies often rely on cytotoxicity assays to estimate genotoxicity. However, measurements of cytotoxicity, a delayed outcome requiring high threshold genotoxicity to induce, does not provide information about the subtle, early genotoxic effects relevant for mechanistic understanding of DNA repair processes. Here describe how to combine two simple procedures for monitoring the presence of DNA damage in individual eukaryotic cells using: (1) the Comet assay for measuring initial DNA breaks and (2) the Micronucleus assay for detecting delayed outcome DNA breaks in dividing cells. We discuss the principles, experimental design considerations and troubleshooting tips for optimizing these methods. They require standard molecular biology instruments and a fluorescent microscope.

  • 269.
    Jiang, Hui
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Xue, Xiaoyu
    Panda, Swarupa
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Kawale, Ajinkya
    Hooy, Richard M.
    Liang, Fengshan
    Sohn, Jungsan
    Sung, Patrick
    Gekara, Nelson O.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death2019Inngår i: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 38, nr 21, artikkel-id e102718Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA repair via homologous recombination (HR) is indispensable for genome integrity and cell survival but if unrestrained can result in undesired chromosomal rearrangements. The regulatory mechanisms of HR are not fully understood. Cyclic GMP‐AMP synthase (cGAS) is best known as a cytosolic innate immune sensor critical for the outcome of infections, inflammatory diseases, and cancer. Here, we report that cGAS is primarily a chromatin‐bound protein that inhibits DNA repair by HR, thereby accelerating genome destabilization, micronucleus generation, and cell death under conditions of genomic stress. This function is independent of the canonical STING‐dependent innate immune activation and is physiologically relevant for irradiation‐induced depletion of bone marrow cells in mice. Mechanistically, we demonstrate that inhibition of HR repair by cGAS is linked to its ability to self‐oligomerize, causing compaction of bound template dsDNA into a higher‐ordered state less amenable to strand invasion by RAD51‐coated ssDNA filaments. This previously unknown role of cGAS has implications for understanding its involvement in genome instability‐associated disorders including cancer.

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  • 270. Jinek, Martin
    et al.
    Chylinski, Krzysztof
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Fonfara, Ines
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hauer, Michael
    Doudna, Jennifer A
    Charpentier, Emmanuelle
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity2012Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 337, nr 6096, s. 816-821Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

  • 271.
    Johansson, Emil
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Caraballo, Remi
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mistry, Nitesh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Zocher, Georg
    Qian, Weixing
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Andersson, C. David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hurdiss, Daniel L.
    Chandra, Naresh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Thompson, Rebecca
    Frängsmyr, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Stehle, Thilo
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections2020Inngår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 15, nr 10, s. 2683-2691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.

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  • 272.
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    RNA thermosensors in bacterial pathogens.2009Inngår i: Bacterial Sensing and Signaling / [ed] Collin M, Schuch R, S. Karger, 2009, Vol. 16, s. 150-160Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    During the course of an infection, a pathogenic bacterium has to sense the environment and adjust its gene expression appropriately. One such environmental cue is the difference in temperature inside and outside the host. RNA thermosensors are structures that can respond to differences in temperature by altering their conformation and thereby allowing/preventing binding of the ribosome to the translational start site. This chapter discusses different types of RNA thermosensors in general and RNA thermosensors known to control virulence gene expression in particular.

  • 273.
    Johansson, Jörgen
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Freitag, Nancy E.
    Regulation of Listeria monocytogenes Virulence2019Inngår i: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 7, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whereas obligate human and animal bacterial pathogens may be able to depend upon the warmth and relative stability of their chosen replication niche, environmental bacteria such as Listeria monocytogenes that harbor the ability to replicate both within animal cells and in the outside environment must maintain the capability to manage life under a variety of disparate conditions. Bacterial life in the outside environment requires adaptation to wide ranges of temperature, available nutrients, and physical stresses such as changes in pH and osmolarity as well as desiccation. Following ingestion by a susceptible animal host, the bacterium must adapt to similar changes during transit through the gastrointestinal tract and overcome a variety of barriers associated with host innate immune responses. Rapid alteration of patterns of gene expression and protein synthesis represent one strategy for quickly adapting to a dynamic host landscape. Here, we provide an overview of the impressive variety of strategies employed by the soil-dwelling, foodborne, mammalian pathogen L. monocytogenes to straddle diverse environments and optimize bacterial fitness both inside and outside host cells.

  • 274.
    Jonsmoen, Unni Lise
    et al.
    Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Ås, Norway.
    Malyshev, Dmitry
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Öberg, Rasmus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Dahlberg, Tobias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Aspholm, Marina E.
    Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Ås, Norway.
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Endospore pili - flexible, stiff and sticky nanofibers2023Inngår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 122, nr 13, s. 2696-2706Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Species belonging to the Bacillus cereus group form endospores (spores) whose surface is decorated with micrometers-long and nanometers-wide endospore appendages (Enas). The Enas have recently been shown to represent a completely novel class of Gram-positive pili. They exhibit remarkable structural properties making them extremely resilient to proteolytic digestion and solubilization. However, little is known about their functional and biophysical properties. In this work, we apply optical tweezers to manipulate and assess how wild type and Ena-depleted mutant spores immobilize on a glass surface. Further, we utilize optical tweezers to extend S-Ena fibers to measure their flexibility and tensile stiffness. Finally, by oscillating single spores, we examine how the exosporium and Enas affect spores’ hydrodynamic properties. Our results show that S-Enas (μm long pili) are not as effective as L-Enas in immobilizing spores to glass surfaces but are involved in forming spore to spore connections, holding the spores together in a gel-like state. The measurements also show that S-Enas are flexible but tensile stiff fibers, which support structural data suggesting that the quaternary structure is composed of subunits arranged in a complex to produce a bendable fiber (helical turns can tilt against each other) with limited axial fiber extensibility. Lastly, the results show that the hydrodynamic drag is 1.5-times higher for wild type spores expressing S- and L-Enas compared to mutant spores expressing only L-Enas or ”bald spores” lacking Ena, and 2-times higher compared to spores of the exosporium deficient strain. This study unveils novel findings on the biophysics of S- and L-Enas, their role in spore aggregation, binding of spores to glass, and their mechanical behavior upon exposure to drag forces.

  • 275.
    Joshi, Bishnu
    et al.
    Department of Medical Biology, Research Group for Host-Microbe Interactions, UiT The Arctic University of Norway, Tromsø, Norway.
    Singh, Bhupender
    Department of Medical Biology, Research Group for Host-Microbe Interactions, UiT The Arctic University of Norway, Tromsø, Norway.
    Nadeem, Aftab
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Askarian, Fatemeh
    Department of Medical Biology, Research Group for Host-Microbe Interactions, UiT The Arctic University of Norway, Tromsø, Norway; Faculty of Chemistry, Biotechnology and Food Science, The Norwegian University of Life Sciences (NMBU), Ås, Norway.
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Johannessen, Mona
    Department of Medical Biology, Research Group for Host-Microbe Interactions, UiT The Arctic University of Norway, Tromsø, Norway.
    Hegstad, Kristin
    Department of Medical Biology, Research Group for Host-Microbe Interactions, UiT The Arctic University of Norway, Tromsø, Norway; Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North-Norway, Tromsø, Norway.
    Transcriptome Profiling of Staphylococcus aureus Associated Extracellular Vesicles Reveals Presence of Small RNA-Cargo2021Inngår i: Frontiers in Molecular Biosciences, E-ISSN 2296-889X, Vol. 7, artikkel-id 566207Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bacterial extracellular vesicles (EVs) have a vital role in bacterial pathogenesis. However, to date, the small RNA-cargo of EVs released by the opportunistic pathogen Staphylococcus aureus has not been characterized. Here, we shed light on the association of small RNAs with EVs secreted by S. aureus MSSA476 cultured in iron-depleted bacteriologic media supplemented with a subinhibitory dosage of vancomycin to mimic infection condition. Confocal microscopy analysis on intact RNase-treated EVs indicated that RNA is associated with EV particles. Transcriptomic followed by bioinformatics analysis of EV-associated RNA revealed the presence of potential gene regulatory small RNAs and high levels of tRNAs. Among the EV-associated enriched small RNAs were SsrA, RsaC and RNAIII. Our finding invites new insights into the potential role of EV-associated RNA as a modulator of host-pathogen interaction.

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  • 276.
    Joshi, Hemant
    et al.
    School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
    Verma, Akanksha
    Department of Botany, MLKPG College, Uttar Pradesh, Balrampur, India.
    Soni, Dharmendra Kumar
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Impact of microbial genomics approaches for novel antibiotic target2019Inngår i: Microbial genomics in sustainable agroecosystems: volume 2 / [ed] Vijay Tripathi; Pradeep Kumar; Pooja Tripathi; Amit Kishore; Madhu Kamle, Springer, 2019, s. 75-88Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Infectious diseases are life-threatening and may lead to high mortality and morbidity rates. The existing danger of an increase and spread of multidrug resistance pathogens is a global concern. Therefore, the designing of novel antibiotics and vaccine to control and eliminate the disease is an utmost requirement. Traditional approaches for screening vaccine and drug targets are time-consuming and have been unsuccessful in controlling the spread of infectious diseases due to several reasons such as altered antigenic diversity, altered virulence potential, and antimicrobial resistance in the infectious agent population. To overcome this problem, there has been a paradigm shift from the conventional to microbial genomics approaches, as the availability of complete genome sequence of pathogenic microorganisms and multiple isolates of the same species provides a wealth of information on nearly all the potential drug targets. Microbial genomics approaches open up new avenues to pursuit novel antimicrobial agents that are highly conserved in a range of microbes, essential for the survival of pathogens and absent in humans. In this chapter, we present an overview of the microbial genomics approaches such as pan-genomics, comparative genomics, functional genomics, structural genomics, transcriptomics, and proteomics used in the discovery and development of novel antibiotics.

  • 277. Jöchl, Christoph
    et al.
    Loh, Edmund
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ploner, Andreas
    Haas, Hubertus
    Hüttenhofer, Alexander
    Development-dependent scavenging of nucleic acids in the filamentous fungus Aspergillus fumigatus.2009Inngår i: RNA biology, ISSN 1555-8584, Vol. 6, nr 2, s. 179-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aspergillus fumigatus is an ubiquitous, filamentous and opportunistic pathogenic fungus which causes fatal invasive aspergillosis among immuno-compromised patients. Since therapeutic strategies are currently limited, the mortality rate of invasive aspergillosis is high and thus, alternative antifungal strategies are required. In this study, we demonstrate that during vegetative growth Aspergillus fumigatus is able to scavenge nucleic acids within its cell wall with accumulation rates of several thousand-fold, compared to the surrounding medium. To investigate, whether nucleic acids, attached to the fungal cell wall, are able to move further into the cytoplasm of fungal cells, we directly applied siRNAs, in the absence of lipo-transfection reagents, to growing A. fumigatus cells. In fact, addition of two 21-nt siRNA duplexes resulted in knock-down of their corresponding target mRNAs, odcA and pyrG, respectively. These findings indicate that RNA interference, mediated by siRNAs, can be used as a fast and efficient tool to investigate the functions of genes within filamentous fungi. In addition, siRNA-based therapies may provide novel approaches for antifungal treatment.

  • 278. Kamps, Dominic
    et al.
    Koch, Johannes
    Juma, Victor O.
    Campillo-Funollet, Eduard
    Graessl, Melanie
    Banerjee, Soumya
    Mazel, Tomas
    Chen, Xi
    Wu, Yao-Wen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Chemical Genomics Centre of the Max-Planck Society, Dortmund, Germany.
    Portet, Stephanie
    Madzvamuse, Anotida
    Nalbant, Perihan
    Dehmelt, Leif
    Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network2020Inngår i: Cell Reports, E-ISSN 2211-1247, Vol. 33, nr 9, artikkel-id 108467Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

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  • 279.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Antypas, Konstantinos
    Sintef Digital, Oslo, Norway.
    Al-Toutanji, Anas
    Biochemical Science and Technology Department, Gaziantep Üniversitesi, Gaziantep, Turkey.
    Suveyd, Usama
    Zooteknik Department, Çukurova Üniversitesi, Gaziantep, Turkey.
    Rafei, Rayane
    Laboratoire Microbiologie Santé et Environnement, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
    Haraoui, Louis-Patrick
    Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
    Elamin, Wael
    G42 Healthcare, Abu Dhabi, United Arab Emirates; Queen Mary University London, London, United Kingdom.
    Hamze, Monzer
    Laboratoire Microbiologie Santé et Environnement, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
    Abbara, Aula
    Department of Infection, Imperial College, London, United Kingdom.
    Rhoads, Daniel D.
    Department of Laboratory Medicine, Cleveland Clinic, OH, Cleveland, United States.
    Pantanowitz, Liron
    Department of Pathology, University of Michigan, MI, Ann Arbor, United States.
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Teleclinical Microbiology: An Innovative Approach to Providing Web-Enabled Diagnostic Laboratory Services in Syria2022Inngår i: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 157, nr 4, s. 554-560Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Telemedicine can compensate for the lack of health care specialists in response to protracted humanitarian crises. We sought to assess the usability of a teleclinical microbiology (TCM) program to provide diagnostic services in a hard-to-reach region of Syria.

    Methods: A semimobile station was equipped with conventional micrograph and macrograph digital imaging systems. An electronic platform (Telemicrobiology in Humanitarian Crises, TmHC) was created to facilitate sharing, interpreting, and storing the results. A pilot study was conducted to identify the bacterial species and antimicrobial susceptibility pattern of 74 urinary clinical isolates. An experience survey was conducted to capture the feedback of 8 participants in the program.

    Results: The TmHC platform (https://sdh.ngo/tmhc/) enabled systematic transmission of the laboratory records and co-interpretation of the results. The isolates were identified as Escherichia coli (n = 61), Klebsiella pneumoniae (n = 12), and Proteus mirabilis(n = 1). All the isolates were multidrug resistant. The performance of our TCM module was rated 4 (satisfying) and 5 (very satisfying) by 6 and 2 users, respectively. Data security of and cost-effectiveness were the main perceived concerns.

    Conclusions: Although we encountered several context-related obstacles, our TCM program managed to reach a highly vulnerable population of 4 million people confined in the northwest region of Syria.

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  • 280.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Dwibedi, Chinmay Kumar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Sjöström, Karin
    Edquist, Petra
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates2016Inngår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, nr 3, s. 1801-1818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to bla(OXA-23) (20 isolates), bla(OXA-24/40-like) (6 isolates), bla(OXA-467) (1 isolate), and ISAba1-bla(OXA-69) (1 isolate). Ceftazidime resistance was associated with bla(PER-7) in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, Delta Tn6279, Ab-ST3- aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite trans-posons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.

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  • 281.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Jolley, Keith A.
    Hall, Ruth M.
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Database for the ampC alleles in Acinetobacter baumannii2017Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 5, artikkel-id e0176695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of >= 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/). Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1), according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

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  • 282.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Khalid, Fizza
    Department of Microbiology, University of Health Sciences, Lahore, Pakistan.
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ahmad, Irfan
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Molecular epidemiology and antimicrobial resistance features of Acinetobacter baumannii clinical isolates from Pakistan2020Inngår i: Annals of Clinical Microbiology and Antimicrobials, E-ISSN 1476-0711, Vol. 19, artikkel-id 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Acinetobacter baumannii is a Gram-negative opportunistic pathogen with a notorious reputation of being resistant to antimicrobial agents. The capability of A. baumannii to persist and disseminate between healthcare settings has raised a major concern worldwide.

    Methods: Our study investigated the antibiotic resistance features and molecular epidemiology of 52 clinical isolates of A. baumannii collected in Pakistan between 2013 and 2015. Antimicrobial susceptibility patterns were determined by the agar disc diffusion method. Comparative sequence analyses of the ampC and blaOXA-51-like alleles were used to assign the isolates into clusters. The whole genomes of 25 representative isolates were sequenced using the MiSeq Desktop Sequencer. Free online applications were used to determine the phylogeny of genomic sequences, retrieve the multilocus sequence types (ST), and detect acquired antimicrobial resistance genes.

    Results: Overall, the isolates were grouped into 7 clusters and 3 sporadic isolates. The largest cluster, Ab-Pak-cluster-1 (blaOXA-66 and ISAba1-ampC-19) included 24 isolates, belonged to ST2 and International clone (IC) II, and was distributed between two geographical far-off cities, Lahore and Peshawar. Ab-Pak-clusters-2 (blaOXA-66, ISAba1-ampC-2), and -3 (blaOXA-66, ISAba1-ampC-20) and the individual isolate Ab-Pak-Lah-01 (ISAba1-blaOXA-66, ISAba1-ampC-2) were also assigned to ST2 and IC II. On the other hand, Ab-Pak-clusters-4 (blaOXA-69, ampC-1), -5 (blaOXA-69, ISAba1-ampC-78), and -6A (blaOXA-371, ISAba1-ampC-3) belonged to ST1, while Ab-Pak-cluster-6B (blaOXA-371, ISAba1-ampC-8) belonged to ST1106, with both ST1 and ST1106 being members of IC I. Five isolates belonged to Ab-Pak-cluster-7 (blaOXA-65, ampC-43). This cluster corresponded to ST158, showed a well-delineated position on the genomic phylogenetic tree, and was equipped with several antimicrobial resistance genes including blaOXA-23 and blaGES-11.

    Conclusions: Our study detected the occurrence of 7 clusters of A. baumannii in Pakistan. Altogether, 6/7 of the clusters and 45/52 (86.5%) of the isolates belonged to IC I (n = 9) or II (n = 36), making Pakistan no exception to the global domination of these two clones. The onset of ST158 in Pakistan marked a geographical dispersal of this clone beyond the Middle East and brought up the need for a detailed characterization.

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  • 283.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Research and Development, KARAHCO, Oslo, Norway.
    Mateo-Estrada, Valeria
    Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
    Castillo-Ramírez, Santiago
    Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
    Higgins, Paul G.
    Institute for Medical Microbiology Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
    Havenga, Benjamin
    Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, South Africa.
    Khan, Wesaal
    Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, South Africa.
    Domingues, Sara
    Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
    Da Silva, Gabriela Jorge
    Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
    Poirel, Laurent
    Medical and Molecular Microbiology, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Fribourg, Switzerland; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland.
    Nordmann, Patrice
    Medical and Molecular Microbiology, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Fribourg, Switzerland; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland.
    Ambrosi, Cecilia
    Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Open University, IRCCS, Rome, Italy.
    Ma, Chaoying
    School of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Belfield, Ireland.
    McClean, Siobhán
    School of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Belfield, Ireland.
    Quiroga, María Paula
    Laboratorio de Investigaciones en Mecanismos de Resistencia a Antibióticos, Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM UBA-CONICET), 1245 Ayacucho, Buenos Aires, Argentina.
    Alvarez, Verónica E.
    Laboratorio de Investigaciones en Mecanismos de Resistencia a Antibióticos, Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM UBA-CONICET), 1245 Ayacucho, Buenos Aires, Argentina.
    Centron, Daniela
    Laboratorio de Investigaciones en Mecanismos de Resistencia a Antibióticos, Instituto de Investigaciones en Microbiología y Parasitología Médica, Facultad de Medicina, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM UBA-CONICET), 1245 Ayacucho, Buenos Aires, Argentina.
    Zarrilli, Raffaele
    Department of Public Health, University of Naples Federico II, Naples, Italy.
    Kenyon, Johanna J.
    Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, QLD, Brisbane City, Australia.
    Russo, Thomas A.
    Veterans Administration Western NY, Healthcare System, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University Buffalo, NY, Buffalo, United States.
    Evans, Benjamin A.
    Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
    Opazo-Capurro, Andres
    Laboratorio de Investigación en Agentes Antibacterianos, Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
    Rafei, Rayane
    Laboratoire Microbiologie Santé et Environnement, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
    Hamze, Monzer
    Laboratoire Microbiologie Santé et Environnement, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
    Daoud, Ziad
    College of Medicine, Central Michigan University, MI, Mount Pleasant, United States; Department of Clinical Microbiology, Michigan Health Clinics, MI, Saginaw, United States.
    Ahmad, Irfan
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Punjab, Lahore, Pakistan.
    Rather, Philip N.
    Department of Microbiology and Immunology, Emory University, School of Medicine, GA, Atlanta, United States; Research Service, Department of Veterans Affairs, Atlanta Veterans Affairs (VA) Medical Center, GA, Decatur, United States.
    Hall, Ruth M.
    School of Life and Environmental Sciences, The University of Sydney, NSW, Sydney, Australia.
    Wilharm, Gottfried
    Robert Koch Institute, Project Group P2 (Acinetobacter baumannii-Biology of a Nosocomial Pathogen), Burgstr 37, Wernigerode, Germany.
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    The acinetobacter baumannii website (ab-web): a multidisciplinary knowledge hub, communication platform, and workspace2023Inngår i: FEMS Microbes, E-ISSN 2633-6685, Vol. 4, artikkel-id xtad009Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Abweb is a species-centric knowledge hub, initially with 10 articles organized into two main sections, 'Overview' and 'Topics', and three themes, 'epidemiology', 'antibiotic resistance', and 'virulence'. The 'workspace' section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas.

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  • 284.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Rafei, Rayane
    Elamin, Wael
    Ghazy, Anan
    Abbara, Aula
    Hamze, Monzer
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Guideline for Urine Culture and Biochemical Identification of Bacterial Urinary Pathogens in Low-Resource Settings2020Inngår i: Diagnostics (Basel), ISSN 2075-4418, Vol. 10, nr 10, artikkel-id 832Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Medical diagnosis in low-resource settings is confronted by the lack of suitable guidelines, protocols and checklists. Online-accessible procedural documents are difficult to find, might be mistranslated or interpreted and usually do not address the needs of developing countries. Urinalysis, one of the most frequently performed diagnostic examinations worldwide, involves a series of tests aiming to detect particular disorders, such as urinary tract infections, kidney disease and diabetes. In this guideline, we present an alternative approach for clinical laboratories with limited resources to identify common bacterial uropathogens. We propose dividing the identification plan into two levels. The implicated pathogen will first be assigned into a bacterial group, basic identification, against which a suitable panel of antimicrobial agents shall be selected for the antimicrobial susceptibility testing (AST). Characterization of the pathogen to the genus or species level, advanced identification, will then be performed to ensure correct reading of the AST results and determine the epidemiology of clinically significant pathogens. Most of the proposed steps in our guideline are tailored to meet the needs of clinical laboratories in low-resource settings. Such guidelines are needed to strengthen the capacity of regional pathology laboratories and to enhance international initiatives on antimicrobial resistance and health equity.

    Fulltekst (pdf)
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  • 285.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Samuelsen, Ørjan
    Zarrilli, Raffaele
    Sahl, Jason W.
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    CRISPR-cas subtype I-Fb in Acinetobacter baumannii: evolution and utilization for strain subtyping2015Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 2, artikkel-id e0118205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clustered regularly interspaced short palindromic repeats (CRISPR) are polymorphic elements found in the genome of some or all strains of particular bacterial species, providing them with a system of acquired immunity against invading bacteriophages and plasmids. Two CRISPR-Cas systems have been identified in Acinetobacter baumannii, an opportunistic pathogen with a remarkable capacity for clonal dissemination. In this study, we investigated the mode of evolution and diversity of spacers of the CRISPR-cas subtype I-Fb locus in a global collection of 76 isolates of A. baumannii obtained from 14 countries and 4 continents. The locus has basically evolved from a common ancestor following two main lineages and several pathways of vertical descent. However, this vertical passage has been interrupted by occasional events of horizontal transfer of the whole locus between distinct isolates. The isolates were assigned into 40 CRISPR-based sequence types (CST). CST1 and CST23-24 comprised 18 and 9 isolates, representing two main sub-clones of international clones CC1 and CC25, respectively. Epidemiological data showed that some of the CST1 isolates were acquired or imported from Iraq, where it has probably been endemic for more than one decade and occasionally been able to spread to USA, Canada, and Europe. CST23-24 has shown a remarkable ability to cause national outbreaks of infections in Sweden, Argentina, UAE, and USA. The three isolates of CST19 were independently imported from Thailand to Sweden and Norway, raising a concern about the prevalence of CST19 in Thailand. Our study highlights the dynamic nature of the CRISPR-cas subtype I-Fb locus in A. baumannii, and demonstrates the possibility of using a CRISPR-based approach for subtyping a significant part of the global population of A. baumannii.

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  • 286.
    Karah, Nabil
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    CRISPR-based subtyping to track the evolutionary history of a global clone of Acinetobacter baumannii2021Inngår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 90, artikkel-id 104774Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acinetobacter baumannii global clone 1 (GC1) is the second most common clone in the global population of A. baumannii isolates and a key cause of hospital-acquired infections. In this study, comparative analysis of the clustered regularly interspaced short palindromic repeats (CRISPR)-based sequence types (CST) was performed to determine the genetic relatedness and track patterns of descent among 187 GC1 isolates, as a complement to the evolutionary inferences from their multilocus sequence types and genome-wide single nucleotide polymorphism (SNP)-based phylogeny. The CST2 cluster, CST2 and all the CSTs descending from CST2, corresponded to GC1 lineage 1. This cluster included 143 of the 187 isolates showing a prevalent geographical distribution worldwide. A well-demarcated group of 13 CSTs, accounting for 33 of the 187 isolates, corresponded to GC1 lineage 2. All the CSTs of this group were characterized by the absence of spacer Ab-18. Many of the GC1 lineage 2 isolates had an epidemiological link to the Middle East and/or were obtained in military healthcare facilities. GC1 lineage 3 was a novel lineage that has so far been limited to Afghanistan, Pakistan and India. Diversification of A. baumannii GC1 into lineages and clades has probably been related to a dynamic expansion after passing a migration bottleneck to enter the hospital environment. We conclude that CRISPR-based subtyping is a convenient method to trace the evolutionary history of particular bacterial clones, such as A. baumannii GC1.

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  • 287. Karamya, Zain Alabadeen
    et al.
    Youssef, Alexey
    Adra, Ali
    Karah, Nabil
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Kanj, Souha S.
    Elamin, Wael
    Al Nahas, Rabiea
    Shaddood, Ali
    Saleh, Ali
    Althiab, Esraa
    Abbara, Aula
    High rates of antimicrobial resistance among clinical isolates from microbiology laboratories in Syria2021Inngår i: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 82, nr 2, s. E8-E10Artikkel i tidsskrift (Fagfellevurdert)
  • 288.
    Karched, Maribasappa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Ihalin, Rikka
    Eneslätt, Kjell
    Zhong, D
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Chen, C
    Asikainen, Sirkka
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Vesicle-independent extracellular release of a proinflammatory outer membrane lipoprotein in free-soluble form2008Inngår i: BMC Microbiology, E-ISSN 1471-2180, Vol. 28, nr 8:18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressively progressing periodontitis. Extracellular release of bacterial outer membrane proteins has been suggested to mainly occur via outer membrane vesicles. This study investigated the presence and conservation of peptidoglycan-associated lipoprotein (AaPAL) among A. actinomycetemcomitans strains, the immunostimulatory effect of AaPAL, and whether live cells release this structural outer membrane lipoprotein in free-soluble form independent of vesicles. RESULTS: The pal locus and its gene product were confirmed in clinical A. actinomycetemcomitans strains by PCR-restriction fragment length polymorphism and immunoblotting. Culturing under different growth conditions revealed no apparent requirement for the AaPAL expression. Inactivation of pal in a wild-type strain (D7S) and in its spontaneous laboratory variant (D7SS) resulted in pleiotropic cellular effects. In a cell culture insert model (filter pore size 0.02 um), AaPAL was detected from filtrates when strains D7S and D7SS were incubated in serum or broth in the inserts. Electron microscopy showed that A. actinomycetemcomitans vesicles (0.05-0.2 um) were larger than the filter pores and that there were no vesicles in the filtrates. The filtrates were immunoblot negative for a cytoplasmic marker, cyclic AMP (cAMP) receptor protein. An ex vivo model indicated cytokine production from human whole blood stimulated by AaPAL. CONCLUSIONS: Free-soluble AaPAL can be extracellularly released in a process independent of vesicles.

  • 289.
    Kauppi, Anna M.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Edin, Alicia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Ziegler, Ingrid
    Mölling, Paula
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Strålin, Kristoffer
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room2016Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 11, nr 1, artikkel-id e0147670Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.

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  • 290.
    Kerkman, Priscilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Dernstedt, Andy
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Tadala, Lalitha
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Mittler, Eva
    Dannborg, Mirjam
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Sundling, Christopher
    Maleki, Kimia T.
    Tauriainen, Johanna
    Tuiskunen-Bäck, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Wigren Byström, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Ocaya, Pauline
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Thunberg, Therese
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Jangra, Rohit K
    Román-Sosa, Gleyder
    Guardado-Calvo, Pablo
    Rey, Feilx A.
    Klingström, Jonas
    Chandran, Kartik
    Puhar, Andrea
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Forsell, Mattias N. E.
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings2021Inngår i: Clinical & Translational Immunology (CTI), E-ISSN 2050-0068, Vol. 10, artikkel-id e1313Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms arenot fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.

    Methods: We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP)and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.

    Results: We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27-IgD- B cells and CD27/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.

    Conclusion:  Our findings demonstrate that thrombocytopenia and kidneydysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infectedindividuals have significantly elevated levels of extracellular ATP incirculation.

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  • 291.
    Khamzeh, Arsham
    et al.
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
    Rudin, Agnes Dahlstrand
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
    Venkatakrishnan, Vignesh
    Department of Rheumatology and Inflammations Research, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, Sweden; Department of Life Sciences, Chalmers University of Technology, Kemigården 4, Gothenburg, Sweden.
    Stylianou, Marios
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sanchez Klose, Felix P.
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Björnsdottir, Halla
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
    Bylund, Johan
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden.
    Christenson, Karin
    Department of Oral Microbiology and Immunology, Sahlgrenska Academy, Institute of Odontology, University of Gothenburg, Medicinaregatan 12A, Gothenburg, Sweden; Department of Oral Microbiology and Immunology, Institute of Odontology, University of Gothenburg, Medicinaregatan 12 A, Gothenburg, Sweden.
    High levels of short-chain fatty acids secreted by Candida albicans hyphae induce neutrophil chemotaxis via free fatty acid receptor 22024Inngår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 115, nr 3, s. 536-546Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicans is polymorphic and switches between different phenotypes (e.g. from yeast form to hyphal form). C. albicans hyphae are invasive and can grow into tissues to eventually reach circulation. During fungal infections, neutrophils in particular play a critical role for the defense, but how neutrophils are directed toward the invasive forms of fungi is less well understood. We set out to investigate possible neutrophil chemoattractants released by C. albicans into culture supernatants. We found that cell-free culture supernatants from the hyphal form of C. albicans induced both neutrophil chemotaxis and concomitant intracellular calcium transients. Size separation and hydrophobic sorting of supernatants indicated small hydrophilic factors as responsible for the activity. Further analysis showed that the culture supernatants contained high levels of short-chain fatty acids with higher levels from hyphae as compared to yeast. Short-chain fatty acids are known neutrophil chemoattractants acting via the neutrophil free fatty acid receptor 2. In line with this, the calcium signaling in neutrophils induced by hyphae culture supernatants was blocked by a free fatty acid receptor 2 antagonist and potently increased in the presence of a positive allosteric modulator. Our data imply that short-chain fatty acids may act as a recruitment signal whereby neutrophils can detect C. albicans hyphae.

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  • 292.
    Khandige, Surabhi
    et al.
    Odense, Denmark.
    Kronborg, Tina
    Odense, Denmark.
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Möller-Jensen, Jakob
    Odense, Denmark.
    sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic Escherichia coli2015Inngår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 11, nr 8, artikkel-id e1005109Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically distinct intracellular and extracellular niches within the urinary tract. This feat requires the timely regulation of gene expression and small RNAs (sRNAs) are known to mediate such rapid adjustments in response to changing environmental cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA chaperone known to facilitate and stabilize sRNA and target mRNA interactions with bacterial cells. The co-immunoprecipitation and high throughput RNA sequencing of Hfq bound sRNAs performed in this study, revealed distinct sRNA profiles in UPEC in the extracellular and intracellular environments. Our findings emphasize the importance of studying regulatory sRNAs in a biologically relevant niche. This strategy also led to the discovery of a novel virulence-associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion of UTI89 to both bladder and kidney cell lines in a manner independent of type-1 fimbriae. We demonstrate PapR mediated post-transcriptional repression of the P-fimbriae phase regulator gene papI and postulate a role for such regulation in fimbrial cross-talk at the population level in UPEC. Our results further implicate the Leucine responsive protein (LRP) as a transcriptional activator regulating PapR expression. Our study reports, for the first time, a role for sRNAs in regulation of P-fimbriae phase variation and emphasizes the importance of studying pathogenesis-specific sRNAs within a relevant biological niche.

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  • 293. Klewer, Laura
    et al.
    Wu, Yao-Wen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Light-Induced Dimerization Approaches to Control Cellular Processes2019Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 25, s. 12452-12463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Light-inducible approaches provide a means to control biological systems with spatial and temporal resolution that is unmatched by traditional genetic perturbations. Recent developments of optogenetic and chemo-optogenetic systems for induced proximity in cells facilitate rapid and reversible manipulation of highly dynamic cellular processes and have become valuable tools in diverse biological applications. New expansions of the toolbox facilitate control of signal transduction, genome editing, "painting" patterns of active molecules onto cellular membranes, and light-induced cell cycle control. A combination of light- and chemically induced dimerization approaches have also seen interesting progress. Herein, an overview of optogenetic systems and emerging chemo-optogenetic systems is provided, and recent applications in tackling complex biological problems are discussed.

    Fulltekst (pdf)
    fulltext
  • 294.
    Klinth, Jeanna E.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Castelain, Mickael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Axner, Ove
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    The Influence of pH on the Specific Adhesion of P Piliated Escherichia coli2012Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38548-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adhesion to host tissues is an initiating step in a majority of bacterial infections. In the case of Gram-negative bacteria this adhesion is often mediated by a specific interaction between an adhesin, positioned at the distal end of bacterial pili, and its receptor on the surface of the host tissue. Furthermore, the rod of the pilus, and particularly its biomechanical properties, is believed to be crucial for the ability of bacteria to withstand external forces caused by, for example, (in the case of urinary tract infections) urinary rinsing flows by redistributing the force to several pili. In this work, the adhesion properties of P-piliated E. coli and their dependence of pH have been investigated in a broad pH range by both the surface plasmon resonance technique and force measuring optical tweezers. We demonstrate that P piliated bacteria have an adhesion ability throughout the entire physiologically relevant pH range (pH 4.5 - 8). We also show that pH has a higher impact on the binding rate than on the binding stability or the biomechanical properties of pili; the binding rate was found to have a maximum around pH 5 while the binding stability was found to have a broader distribution over pH and be significant over the entire physiologically relevant pH range. Force measurements on a single organelle level show that the biomechanical properties of P pili are not significantly affected by pH.

    Fulltekst (pdf)
    fulltext
  • 295.
    Klinth, Jeanna E
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Pinkner, Jerome S
    Hultgren, Scott J
    Almqvist, Fredrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Axner, Ove
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections?2012Inngår i: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 41, nr 3, s. 285-295Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gram-negative bacteria often initiate their colonization by use of extended attachment organelles, so called pili. When exposed to force, the rod of helix-like pili has been found to be highly extendable, mainly attributed to uncoiling and recoiling of its quaternary structure. This provides the bacteria with the ability to redistribute an external force among a multitude of pili, which enables them to withstand strong rinsing flows, which, in turn, facilitates adherence and colonization processes critical to virulence. Thus, pili fibers are possible targets for novel antibacterial agents. By use of a substance that compromises compliance of the pili, the ability of bacteria to redistribute external forces can be impaired, so they will no longer be able to resist strong urine flow and thus be removed from the host. It is possible such a substance can serve as an alternative to existing antibiotics in the future or be a part of a multi-drug. In this work we investigated whether it is possible to achieve this by targeting the recoiling process. The test substance was purified PapD. The effect of PapD on the compliance of P pili was assessed at the single organelle level by use of force-measuring optical tweezers. We showed that the recoiling process, and thus the biomechanical compliance, in particular the recoiling process, can be impaired by the presence of PapD. This leads to a new concept in the search for novel drug candidates combating uropathogenic bacterial infections-"coilicides", targeting the subunits of which the pilus rod is composed.

    Fulltekst (pdf)
    fulltext
  • 296.
    Koller, Timm O.
    et al.
    Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany.
    Turnbull, Kathryn Jane
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
    Vaitkevicius, Karolis
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Crowe-Mcauliffe, Caillan
    Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany.
    Roghanian, Mohammad
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark; Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Bulvas, Ondřej
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nam. 2, Prague 6, Czech Republic; Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technicka 5, Prague 6, Czech Republic.
    Nakamoto, Jose A.
    Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Kurata, Tatsuaki
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Julius, Christina
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Atkinson, Gemma C.
    Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Department of Experimental Medical Science, Lund University, Lund, Sweden; University of Tartu, Institute of Technology, Tartu, Estonia.
    Wilson, Daniel N.
    Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany.
    Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes2022Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 50, nr 19, s. 11285-11300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.

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    fulltext
  • 297.
    Kouidmi, Imène
    et al.
    Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, QC, Montreal, Canada.
    Alvarez, Laura
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Collet, Jean François
    De Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Paradis-Bleau, Catherine
    Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, QC, Montreal, Canada.
    The chaperone activities of dsbg and spy restore peptidoglycan biosynthesis in the elyC mutant by preventing envelope protein aggregation2018Inngår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 200, nr 19, artikkel-id e00245Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peptidoglycan (PG) is the main structural component of bacterial envelopes. It protects bacterial cells against variations in osmotic pressure and cell lysis. The newly discovered Escherichia coli factor ElyC has been shown to be important for peptidoglycan biosynthesis at low temperatures. PG production in ΔelyC mutant cells is totally blocked after a few hours of growth at 21°C, triggering cell lysis. In this study, we took a candidate approach to identify genetic suppressors of the ΔelyC mutant cell lysis phenotype. We identified the periplasmic proteins DsbG and Spy as multicopy suppressors and showed that their overproduction restores PG biosynthesis in the ΔelyC mutant. Interestingly, we found that DsbG acts by a novel mechanism, which is independent of its known reductase activity and substrates. DsbG, like Spy, acts as a chaperone to reduce the amounts of protein aggregates in the envelopes of ΔelyC cells. In fact, we found that the amount of protein aggregates was greater in the ΔelyC mutant than in the wild type. Taken together, our results show a protein-folding defect in the envelope compartments of ΔelyC cells that blocks PG production, and they reveal a new physiological activity of DsbG.

    IMPORTANCE: Peptidoglycan biosynthesis is a dynamic and well-controlled pathway. The molecular assembly of PG and the regulatory pathways ensuring its maintenance are still not well understood. Here we studied the newly discovered Escherichia coli factor ElyC, which is important for PG biosynthesis at low temperatures. We revealed an important protein-folding defect in the ΔelyC mutant and showed that overproduction of the periplasmic chaperone DsbG or Spy was sufficient to correct the protein-folding defect and restore PG biosynthesis. These results show that the PG defect in the absence of ElyC is caused, at least in part, by a protein-folding problem in the cell envelope. Furthermore, we showed, for the first time, that the periplasmic protein DsbG has chaperone activity in vivo.

  • 298.
    Kouokam, J Clavin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Fällman, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Dobrindt, Ulrich
    Hacker, Jörg
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Active cytotoxic necrotizing factor 1 associated with outer membrane vesicles from uropathogenic Escherichia coli.2006Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, nr 4, s. 2022-2030Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cytotoxic necrotizing factor type 1 (CNF1) is one of the virulence factors produced by uropathogenic Escherichia coli (UPEC). How this toxin is translocated from the bacterial cytoplasm to the surrounding environment is not well understood. Our data suggest that CNF1 may be regarded as a secreted protein, since it could be detected in culture supernatants. Furthermore, we found that CNF1 was tightly associated to outer membrane vesicles, suggesting that such vesicles play a role in the secretion of this protein. Interestingly, vesicle samples containing CNF1 could exert the effects known for this protein on HeLa cell cultures, showing that CNF1 is transported by vesicles in its active form. Taken together, our results strongly suggest that outer membrane vesicles could be a means for the bacteria to deliver CNF1 to the environment and to the infected tissue. In addition, our results indicate that the histone-like nucleoid structuring protein H-NS has a role in the downregulation of CNF1 production and that it affects the outer membrane vesicle release in UPEC strain J96.

  • 299.
    Kowalczyk, Manuela
    et al.
    Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
    Kamps, Dominic
    Department of Chemistry and Chemical Biology and Department of Systemic Cell Biology, TU Dortmund University and Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
    Wu, Yao-Wen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Dehmelt, Leif
    Department of Chemistry and Chemical Biology and Department of Systemic Cell Biology, TU Dortmund University and Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.
    Nalbant, Perihan
    Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
    Monitoring the Response of Multiple Signal Network Components to Acute Chemo-Optogenetic Perturbations in Living Cellsope2022Inngår i: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 23, nr 4, artikkel-id e202100582Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cells process information via signal networks that typically involve multiple components which are interconnected by feedback loops. The combination of acute optogenetic perturbations and microscopy-based fluorescent response readouts enables the direct investigation of causal links in such networks. However, due to overlaps in spectra of photosensitive and fluorescent proteins, current approaches that combine these methods are limited. Here, we present an improved chemo-optogenetic approach that is based on switch-like perturbations induced by a single, local pulse of UV light. We show that this approach can be combined with parallel monitoring of multiple fluorescent readouts to directly uncover relations between signal network components. We present the application of this technique to directly investigate feedback-controlled regulation in the cell contraction signal network that includes GEF-H1, Rho and Myosin, and functional interactions of this network with tumor relevant RhoA G17 mutants.

    Fulltekst (pdf)
    fulltext
  • 300.
    Krajewski, Stefanie Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Ignatov, Dmitry
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Johansson, Jörgen
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Two Are Better Than One: Dual Targeting of Riboswitches by Metabolite Analogs2017Inngår i: Cell Chemical Biology, ISSN 2451-9456, E-ISSN 2451-9448, Vol. 24, nr 5, s. 535-537Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this issue of Cell Chemical Biology, Wang et al. (2017) examine the effect of the novel synthetic molecule ribocil-C and the natural compound roseoflavin in Gram-positive pathogens. In methicillin-resistant Staphylococcus aureus (MRSA), ribocil-C and roseoflavin target two autonomous riboswitches simultaneously, thereby inhibiting de novo synthesis and uptake of riboflavin.

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