umu.sePublications
Change search
Refine search result
34567 251 - 300 of 328
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 251.
    Rydén, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Björk, Rafael
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Schäfer, Martina L
    Lundström, Jan O
    Petersén, Bodil
    Lindblom, Anders
    Forsman, Mats
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence2012In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 205, no 2, p. 297-304Article in journal (Refereed)
    Abstract [en]

    Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data.

    Methods. A prediction model for mosquito abundance was built using weather and mosquito catch data. Then a negative binomial regression model based on the predicted mosquito abundance and local weather data was built to predict annual numbers of humans contracting tularemia in Dalarna County, Sweden.

    Results. Three hundred seventy humans were diagnosed with tularemia between 1981 and 2007, 94% of them during 7 summer outbreaks. Disease transmission was concentrated along rivers in the area. The predicted mosquito abundance was correlated (0.41, P < .05) with the annual number of human cases. The predicted mosquito peaks consistently preceded the median onset time of human tularemia (temporal correlation, 0.76; P < .05). Our final predictive model included 5 environmental variables and identified 6 of the 7 outbreaks.

    Conclusions. This work suggests that a high prevalence of mosquitoes in late summer is a prerequisite for outbreaks of tularemia in a tularemia-endemic boreal forest area of Sweden and that environmental variables can be used as risk indicators.

  • 252.
    Röhm, Marc
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Grimm, Melissa J.
    D'Auria, Anthony C.
    Almyroudis, Nikolaos G.
    Segal, Brahm H.
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis2014In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, no 5, p. 1766-1777Article in journal (Refereed)
    Abstract [en]

    NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates. Aspergillus species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in Aspergillus fumigatus pneumonia. Oropharyngeal instillation of live Aspergillus hyphae induced neutrophilic pneumonitis in both wildtype and NADPH oxidase-deficient (p47(phox-/-)) mice which had resolved in wild-type mice by day 5 but progressed in p47(phox-/-) mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47(phox-/-) mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase in vivo and ex vivo. In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of Aspergillus hyphae and generation of NETs in vivo. We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance.

  • 253. Saffari, Fereshteh
    et al.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Karmostaji, Afsaneh
    Azimabad, Fahimeh Bahadori
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Significant spread of extensively drug-resistant Acinetobacter baumannii genotypes of clonal complex 92 among intensive care unit patients in a university hospital in southern Iran2017In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 11, p. 1656-1662Article in journal (Refereed)
    Abstract [en]

    Purpose: Infections associated with Acinetobacter baumannii represent an increasing threat in healthcare settings. Therefore, we investigated the epidemiological relationship between clinical isolates of A. baumannii obtained from patients in a university hospital in Bandar Abbas in southern Iran.

    Methodology: Sixty-four consecutive non-duplicate clinical isolates collected during 2014–2015 were subjected to susceptibility testing, clonal relationship analysis using PFGE, multilocus variable-number tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST), and examined for the presence of carbapenemases and integrons.

    Results: Almost all A. baumannii isolates were extensively drug-resistant (XDR; 98 %) and carried an OXA carbapenemase gene (bla OXA-23-like; 98 %) and class 1 integrons (48 %). PFGE and MLST analysis identified three major genotypes, all belonging to clonal complex 92 (CC92): sequence type 848 (ST848) (n=23), ST451 (n=16) and ST195 (n=8). CC92 has previously been documented in the hospital setting in northern Iran, and ST195 has been reported in Arab States of the Persian Gulf. These data suggest national and global transmission of A. baumannii CC92.

    Conclusion: This report demonstrates the occurrence and potential spread of closely related XDR genotypes of A. baumannii CC92 within a university hospital in southern Iran. These genotypes were found in the majority of the investigated isolates, showed high prevalence of blaOXA-23 and integron class 1, and were associated with stay in the intensive care unit. Very few treatment options remain for healthcare-adapted XDR A. baumannii, and hence effective measures are desperately needed to reduce the spread of these strains and resultant infections in the healthcare setting.

  • 254. Saffari, Fereshteh
    et al.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gurram, Bharat Kumar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Edebro, Helen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hojabri, Zoya
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Molecular and Phenotypic Characterization of Multidrug-Resistant Clones of Staphylococcus epidermidis in Iranian Hospitals: Clonal Relatedness to Healthcare-Associated Methicillin-Resistant Isolates in Northern Europe2016In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 22, no 7, p. 570-577Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the molecular epidemiology of Staphylococcus epidermidis in Iranian hospitals and to compare the genotypes with a previously characterized collection of >1,300 S. epidermidis isolates of nosocomial and community origin from Northern Europe, Australia, and USA. In total, 82 clinical S. epidermidis isolates from three Iranian hospitals were examined by multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome mec (SCCmec) typing. In addition, antimicrobial susceptibility, the presence of the ica operon, and the predilection to biofilm formation were assessed. Three predominant PFGE clones were found. The PFGE patterns of the most common sequence type (PFGE type 040-ST2) showed 80% similarity to multidrug-resistant S. epidermidis (MDRSE) clinical isolates from eight hospitals in Northern Europe. The second most common (PFGE 024-ST22) showed an unique PFGE pattern, whereas the third most predominant genotype (PFGE 011-ST5) proved indistinguishable to the PFGE Co-ST5 identified in five hospitals in Northern Europe. In conclusion, the study documented the dissemination of three MDRSE clones within and between hospitals in Iran and revealed an intercontinental spread of two clonal multidrug-resistant lineages (ST2 and ST5) in the hospital environment. Isolates of the predominant clones were significantly more frequently associated with multidrug-resistance and biofilm formation compared to nonclonal isolates. Further studies are needed to explore and characterize the genetic traits that enable these successful MDRSE clones to persist and disseminate worldwide in the healthcare settings.

  • 255. Sahdo, Berolla
    et al.
    Särndahl, Eva
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Söderquist, Bo
    Propionibacterium acnes activates caspase-1 in human neutrophils2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 7, p. 652-663Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a Gram-positive, slow-growing, anaerobic bacillus, predominantly found as a commensal on the skin and mucous membranes of adults. It is, however, also considered an opportunistic pathogen; mostly associated with acne vulgaris, but rarely also with severe infections such as infective endocarditis, prosthetic joint infections, and deep sternal wound infections following cardiothoracic surgery. In addition, P. acnes has recently been found in high frequency in prostate tissue from patients with prostatitis and prostate cancer. The NOD-like receptors (NLR) act as intracellular sensors of microbial components, and a number of various bacteria have been found to induce assembling and activation of NLR-inflammasomes; leading to a pro-inflammatory response. The inflammasome-mediated formation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 involves the auto-proteolytic maturation of caspase-1. This study investigated if P. acnes activates inflammasomes. Propionibacterium acnes isolates (n = 29) with diverse origin were used as stimuli for peripheral leukocytes obtained from blood donors (BDs). The activity of inflammasomes was determined by measuring caspase-1 by flow cytometry and cytokine production by ELISA. A significant amount of caspase-1 was found in neutrophils upon P. acnes stimulation, whereas only a modest activation was seen in monocytes. The activation was mainly produced by components of the bacterial cell and no exo-products, because heat-killed and live bacteria caused high activation of caspase-1 as well as cytokine production, whereas the bacterial supernatant elicited minor effect. The response among different BDs varied significantly, almost fivefold. In addition, P. acnes of various origins showed considerable variation, however, the commensal isolates showed a stronger response compared with the invasive. In conclusion, although regarded as a harmless commensal of the skin, P. acnes strongly activates the inflammasome of human peripheral neutrophils.

  • 256. Sang, Rosemary
    et al.
    Arum, Samwel
    Chepkorir, Edith
    Mosomtai, Gladys
    Tigoi, Caroline
    Sigei, Faith
    Lwande, Olivia Wesula
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Landmann, Tobias
    Affognon, Hippolyte
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 2, article id e0005341Article in journal (Refereed)
    Abstract [en]

    Background Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity. Methodology Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo), cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis. Findings Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes. Conclusion This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases.

  • 257.
    Schliamser, Silvia E.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Neurotoxicity of β-lactam antibiotics: experimental kinetic and neurophysiological studies1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The neurotoxic potential of intravenous administered benzylpenicillin (BPC) was studied in rabbits with intact blood-CNS barriers and rabbits with experimental E. coli meningitis. At onset of epileptogenic EEG activity or seizures, serum, CSF and brain tissue were collected for assay of BPC. Based on the fact that, in tissues, BPC seems to remain extracellularly, brain concentrations of BPC were expressed as brain tissue fluid (BTF) levels, calculated as lOx the concentration in whole brain tissue. Neurotoxicity could be precipitated in all rabbits. In normal rabbits BTF levels of BPC were considerably higher than those in CSF indicating a better penetration across the blood-brain barrier (BBB). BPC penetrated better to CSF and BTF in meningitic rabbits than in normal controls, suggesting some degree of damage of the BBB concomitant with meningeal inflammation. E. coli meningitis did not increase the neurotoxicity of BPC. In control rabbits the intracistemal injection of saline resulted in some degree of pleocytosis. Unmanipulated animals are therefore preferable as controls. Epileptogenic EEG-changes was the most precise of the two variables used for demonstration of neurotoxicity. EEG-changes were therefore used as neurotoxicity criterion in the following rabbit experiments. To evaluate the effect of uraemia alone and uraemia plus meningitis on the neurotoxity of BPC in rabbits, cephaloridine was used to induce uraemia. Meningitis was induced by intracistemal inoculation of a cephalosporinresistant strain of E. cloacae. Untreated  rabbits were used as controls. Uraemia resulted in increased BTF penetration of BPC, possibly explained by permeability changes in the BBB and/or decreased binding of BPC to albumin. Uraemia did not result in increased penetration of BPC into the CSF of non-meningitic rabbits. Uraemic non-meningitic rabbits had the highest BTF levels of BPC at the criterion, indicating that cephaloridine-induced renal failure increased the epileptogenic threshold in these rabbits. The combination of uraemia and meningitis increased the neurotoxicity of BPC since the criterion was reached at considerably lower BTF levels of BPC. Meningitis, either alone or together with uraemia, did not increase the neurotoxicity in comparison to control rabbits. Higher BTF levels of BPC were found in meningitic rabbits than in controls with intact blood-CNS barriers at onset of EEG-changes. In all groups of rabbits there was a pronounced variability of BPC levels in the CSF while the intra-group variations in BTF levels were much smaller. Thus, BTF and not CSF levels were decisive for the neurotoxicity of BPC. Using   the same EEG-model, the neurotoxic potential of imipenem/cilastatin (I) and a new penem derivative, FCE 22101 were compared in a cross-over study. Both I and FCE 22101 were significantly more neurotoxic than BPC. While BTF levels of the three antibiotics could be detected in all tested rabbits, detectable CSF levels were only found in one of twelve rabbits treated with I or FCE 22101, indicating that BTF concentrations rather than CSF ones are decisive for neurotoxicity of ß-lactam antibiotics. The EEG-model used was found to be a suitable model for cross-over studies of intravenously administered antibiotics. Using the "silent-second" as EEG-threshold, a CNS interaction between intraperitoneally administered BPC and intravenous thiopental was demonstrated in rats. The most probably site for this interaction is the organic acid transport system out of the CNS. Thiopental distribution in the rat brain seemed to depend not only on its lipid solubility.

  • 258.
    Schröder, Björn
    et al.
    Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Birchenough, George M H
    Ståhlman, Marcus
    Arike, Liisa
    Johansson, Malin E V
    Hansson, Gunnar C
    Bäckhed, Fredrik
    Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration2018In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 23, no 1, p. 27-40.e7Article in journal (Refereed)
    Abstract [en]

    Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.

  • 259. Seiwert, Nina
    et al.
    Neitzel, Carina
    Stroh, Svenja
    Frisan, Teresa
    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
    Audebert, Marc
    Toulany, Mahmoud
    Kaina, Bernd
    Fahrer, Jörg
    AKT2 suppresses pro-survival autophagy triggered by DNA double-strand breaks in colorectal cancer cells2017In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 8, no 8, article id e3019Article in journal (Refereed)
    Abstract [en]

    DNA double-strand breaks (DSBs) are critical DNA lesions, which threaten genome stability and cell survival. DSBs are directly induced by ionizing radiation (IR) and radiomimetic agents, including the cytolethal distending toxin (CDT). This bacterial genotoxin harbors a unique DNase-I-like endonuclease activity. Here we studied the role of DSBs induced by CDT and IR as a trigger of autophagy, which is a cellular degradation process involved in cell homeostasis, genome protection and cancer. The regulatory mechanisms of DSB-induced autophagy were analyzed, focusing on the ATM-p53-mediated DNA damage response and AKT signaling in colorectal cancer cells. We show that treatment of cells with CDT or IR increased the levels of the autophagy marker LC3B-II. Consistently, an enhanced formation of autophagosomes and a decrease of the autophagy substrate p62 were observed. Both CDT and IR concomitantly suppressed mTOR signaling and stimulated the autophagic flux. DSBs were demonstrated as the primary trigger of autophagy using a DNase I-defective CDT mutant, which neither induced DSBs nor autophagy. Genetic abrogation of p53 and inhibition of ATM signaling impaired the autophagic flux as revealed by LC3B-II accumulation and reduced formation of autophagic vesicles. Blocking of DSB-induced apoptotic cell death by the pan-caspase inhibitor Z-VAD stimulated autophagy. In line with this, pharmacological inhibition of autophagy increased cell death, while ATG5 knockdown did not affect cell death after DSB induction. Interestingly, both IR and CDT caused AKT activation, which repressed DSB-triggered autophagy independent of the cellular DNA-PK status. Further knockdown and pharmacological inhibitor experiments provided evidence that the negative autophagy regulation was largely attributable to AKT2. Finally, we show that upregulation of CDT-induced autophagy upon AKT inhibition resulted in lower apoptosis and increased cell viability. Collectively, the findings demonstrate that DSBs trigger pro-survival autophagy in an ATM- and p53-dependent manner, which is curtailed by AKT2 signaling.

  • 260. Semenza, Jan C.
    et al.
    Lindgren, Elisabet
    Balkanyi, Laszlo
    Espinosa, Laura
    Almqvist, My S.
    Penttinen, Pasi
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Determinants and Drivers of Infectious Disease Threat Events in Europe2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 4, p. 581-589Article in journal (Refereed)
    Abstract [en]

    Infectious disease threat events (IDTEs) are increasing in frequency worldwide. We analyzed underlying drivers of 116 IDTEs detected in Europe during 2008-2013 by epidemic intelligence at the European Centre of Disease Prevention and Control. Seventeen drivers were identified and categorized into 3 groups: globalization and environment, sociodemographic, and public health systems. A combination of >= 2 drivers was responsible for most IDTEs. The driver category globalization and environment contributed to 61% of individual IDTEs, and the top 5 individual drivers of all IDTEs were travel and tourism, food and water quality, natural environment, global trade, and climate. Hierarchical cluster analysis of all drivers identified travel and tourism as a distinctly separate driver. Monitoring and modeling such disease drivers can help anticipate future IDTEs and strengthen control measures. More important, intervening directly on these underlying drivers can diminish the likelihood of the occurrence of an IDTE and reduce the associated human and economic costs.

  • 261. Semenza, Jan C.
    et al.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Penttinen, Pasi
    Lindgren, Elisabet
    Observed and projected drivers of emerging infectious diseases in Europe2016In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1382, p. 73-83Article in journal (Refereed)
    Abstract [en]

    Emerging infectious diseases are of international concern because of the potential for, and impact of, pandemics; however, they are difficult to predict. To identify the drivers of disease emergence, we analyzed infectious disease threat events (IDTEs) detected through epidemic intelligence collected at the European Centre for Disease Prevention and Control (ECDC) between 2008 and 2013, and compared the observed results with a 2008 ECDC foresight study of projected drivers of future IDTEs in Europe. Among 10 categories of IDTEs, foodborne and waterborne IDTEs were the most common, vaccine-preventable IDTEs caused the highest number of cases, and airborne IDTEs caused the most deaths. Observed drivers for each IDTE were sorted into three main groups: globalization and environmental drivers contributed to 61% of all IDTEs, public health system drivers contributed to 21%, and social and demographic drivers to 18%. A multiple logistic regression analysis showed that four of the top five drivers for observed IDTEs were in the globalization and environment group. In the observational study, the globalization and environment group was related to all IDTE categories, but only to five of eight categories in the foresight study. Directly targeting these drivers with public health interventions may diminish the chances of IDTE occurrence from the outset.

  • 262. Sendi, P
    et al.
    Christensson, B
    Uçkay, I
    Trampuz, A
    Achermann, Y
    Boggian, K
    Svensson, D
    Widerström, Micael
    Department of Infectious Diseases, Östersund Hospital, Östersund, Sweden.
    Zimmerli, W
    Group B streptococcus in prosthetic hip and knee joint-associated infections2011In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 79, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    The incidence of invasive group B streptococcus (GBS) infections in non-pregnant adults is increasing. Little is known about GBS in periprosthetic joint infections (PJIs). We aimed to analyse the clinical presentation of GBS PJI and its treatment in association with the outcome. The characteristics of 36 GBS PJIs collected from 10 centres were investigated. In 34 episodes, follow-up examination of ≥ 2 years was available, allowing treatment and outcome analysis. Most infections (75%) occurred ≥ 3 months after implantation. Most patients (91%) had at least one comorbidity; 69% presented with acute symptoms and 83% with damaged periprosthetic soft tissue. In 20 of 34 episodes debridement and retention of implant was attempted, but in five of these the prosthesis was ultimately removed. Hence, in 19 (56%) episodes, the implant was removed, including 14 immediate removals. In four episodes the removal was permanent. Penicillin derivatives and clindamycin were the most common antimicrobials administered (68%). In 94% the infection was cured, and in 82% functional mobility preserved. Debridement with implant retention was successful if the duration of symptoms was short, the prosthesis stable, and the tissue damage minor (10/10 vs 3/10 episodes, P = 0.003). Surgery that complied with a published algorithm was associated with a favourable outcome (P = 0.049).

  • 263. Seruyange, Eric
    et al.
    Ljungberg, Karl
    Muvunyi, Claude Mambo
    Gahutu, Jean Bosco
    Katare, Swaibu
    Nyamusore, Jose
    Yongdae, Kwon
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Norder, Helene
    Liljestrom, Peter
    Bergstrom, Tomas
    Seroreactivity to Chikungunya and West Nile Viruses in Rwandan Blood Donors2019In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 19, no 10, p. 731-740Article in journal (Refereed)
    Abstract [en]

    Introduction: Chikungunya virus (CHIKV) and West Nile virus (WNV) have previously been reported from several African countries, including those bordering Rwanda where they may have originated. However, there have been no serosurveillance reports from Rwanda regarding these two viral pathogens. In this article, we present the first study of immunoglobulin G (IgG) seroreactivity of CHIKV and WNV in Rwandan blood donor samples. Methods: Blood donors from Rwanda (n = 874) and Sweden (n = 199) were tested for IgG reactivity against CHIKV, using an in-house enzyme-linked immunosorbent assay with the E1 envelope protein fused with p62 as antigen, and against WNV using a commercial kit. Data on mosquito distribution were obtained from the 2012 assessment of yellow fever virus circulation in Rwanda. Results: Seroreactivity to CHIKV was high in Rwanda (63.0%), when compared with Swedish donors, where only 8.5% were IgG positive. However, a cross-reactivity to O'nyong'nyong virus in neutralization test was noted in Rwandan donors. No significant difference in WNV seroreactivity was found (10.4% for Rwandan and 14.1% for Swedish donors). The relatively high seroreactivity to WNV among Swedish donors could partly be explained by cross-reactivity with tick-borne encephalitis virus prevalent in Sweden. Donors from the Eastern Province of Rwanda had the highest IgG reactivity to the two investigated viruses (86.7% for CHIKV and 33.3% for WNV). Five genera of mosquitoes were found in Rwanda where Culex was the most common (82.5%). The vector of CHIKV, Aedes, accounted for 9.6% of mosquitoes and this species was most commonly found in the Eastern Province. Conclusions: Our results showed high seroreactivity to CHIKV in Rwandan donors. The highest IgG reactivity to CHIKV, and to WNV, was found in the Eastern Province, the area reporting the highest number of mosquito vectors for these two viruses. Infection control by eliminating mosquito-breeding sites in population-dense areas is recommended, especially in eastern Rwanda.

  • 264. Sharma, Sumit
    et al.
    Hagbom, Marie
    Carlsson, Beatrice
    Ohd, Joanna Nederby
    Insulander, Mona
    Eriksson, Ronnie
    Simonsson, Magnus
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Department of Communicable Disease Control and Prevention, Stockholm County Council, Stockholm, Sweden.
    Nordgren, Johan
    Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak2019In: Food and Environmnetal Virology, ISSN 1867-0334, E-ISSN 1867-0342Article in journal (Refereed)
    Abstract [en]

    Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain.

  • 265.
    Silver, Jim
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Islam, Bakhtiar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Replication-competent adenovirus 11p GFP vector (RCAd11pGFP) enhances CEACAM6 expression in colon cancer cellsManuscript (preprint) (Other academic)
  • 266. Sironen, Tarja
    et al.
    Sane, Jussi
    Lokki, Marja-Liisa
    Meri, Seppo
    Andersson, Leif C.
    Hautala, Timo
    Kauma, Heikki
    Vuorinen, Sakari
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Vaheri, Antti
    Fatal Puumala Hantavirus Disease: Involvement of Complement Activation and Vascular Leakage in the Pathobiology2017In: Open Forum Infectious Diseases, ISSN 2328-8957, Vol. 4, no 4, article id ofx229Article in journal (Refereed)
    Abstract [en]

    The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood, and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.

  • 267. Sjöwall, J
    et al.
    Carlsson, A
    Vaarala, O
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ernerudh, J
    Forsberg, P
    Ekerfelt, C
    Innate immune responses in Lyme borreliosis: enhanced tumour necrosis factor-alpha and interleukin-12 in asymptomatic individuals in response to live spirochetes2005In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed)
    Abstract [en]

    Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1 beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease.

  • 268. Skog, Lars
    et al.
    Linde, Annika
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hauska, Hans
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Spatiotemporal characteristics of pandemic influenza2014In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 14, p. 378-Article in journal (Refereed)
    Abstract [en]

    Background: Prediction of timing for the onset and peak of an influenza pandemic is of vital importance for preventive measures. In order to identify common spatiotemporal patterns and climate influences for pandemics in Sweden we have studied the propagation in space and time of A(H1N1)pdm09 (10,000 laboratory verified cases), the Asian Influenza 1957-1958 (275,000 cases of influenza-like illness (ILI), reported by local physicians) and the Russian Influenza 1889-1890 (32,600 ILI cases reported by physicians shortly after the end of the outbreak). Methods: All cases were geocoded and analysed in space and time. Animated video sequences, showing weekly incidence per municipality and its geographically weighted mean (GWM), were created to depict and compare the spread of the pandemics. Daily data from 1957-1958 on temperature and precipitation from 39 weather stations were collected and analysed with the case data to examine possible climatological effects on the influenza dissemination. Results: The epidemic period lasted 11 weeks for the Russian Influenza, 10 weeks for the Asian Influenza and 9 weeks for the A(H1N1)pdm09. The Russian Influenza arrived in Sweden during the winter and was immediately disseminated, while both the Asian Influenza and the A(H1N1)pdm09 arrived during the spring. They were seeded over the country during the summer, but did not peak until October-November. The weekly GWM of the incidence moved along a line from southwest to northeast for the Russian and Asian Influenza but northeast to southwest for the A(H1N1)pdm09. The local epidemic periods of the Asian Influenza were preceded by falling temperature in all but one of the locations analysed. Conclusions: The power of spatiotemporal analysis and modeling for pandemic spread was clearly demonstrated. The epidemic period lasted approximately 10 weeks for all pandemics. None of the pandemics had its epidemic period before late autumn. The epidemic period of the Asian Influenza was preceded by falling temperatures. Climate influences on pandemic spread seem important and should be further investigated.

  • 269.
    Song, Tianyan
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Duperthuy, Marylise
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sub-Optimal Treatment of Bacterial Biofilms2016In: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 5, no 2, article id 23Article, review/survey (Refereed)
    Abstract [en]

    Bacterial biofilm is an emerging clinical problem recognized in the treatment of infectious diseases within the last two decades. The appearance of microbial biofilm in clinical settings is steadily increasing due to several reasons including the increased use of quality of life-improving artificial devices. In contrast to infections caused by planktonic bacteria that respond relatively well to standard antibiotic therapy, biofilm-forming bacteria tend to cause chronic infections whereby infections persist despite seemingly adequate antibiotic therapy. This review briefly describes the responses of biofilm matrix components and biofilm-associated bacteria towards sub-lethal concentrations of antimicrobial agents, which may include the generation of genetic and phenotypic variabilities. Clinical implications of bacterial biofilms in relation to antibiotic treatments are also discussed.

  • 270.
    Song, Tianyan
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sabharwal, Dharmesh
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Gurung, Jyoti Mohan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Cheng, Andrew T.
    Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America.
    Sjöström, Annika E.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Yildiz, Fitnat H.
    Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Vibrio cholerae Utilizes Direct sRNA Regulation in Expression of a Biofilm Matrix Protein2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, article id e101280Article in journal (Refereed)
    Abstract [en]

    Vibrio cholerae biofilms contain exopolysaccharide and three matrix proteins RbmA, RbmC and Bap1. While much is known about exopolysaccharide regulation, little is known about the mechanisms by which the matrix protein components of biofilms are regulated. VrrA is a conserved, 140-nt sRNA of V. cholerae, whose expression is controlled by sigma factor sigma(E). In this study, we demonstrate that VrrA negatively regulates rbmC translation by pairing to the 5' untranslated region of the rbmC transcript and that this regulation is not stringently dependent on the RNA chaperone protein Hfq. These results point to VrrA as a molecular link between the sigma(E)-regulon and biofilm formation in V. cholerae. In addition, VrrA represents the first example of direct regulation of sRNA on biofilm matrix component, by-passing global master regulators.

  • 271. Sothiselvam, Shanmugapriya
    et al.
    Liu, Bo
    Han, Wei
    Ramu, Haripriya
    Klepacki, Dorota
    Atkinson, Gemma Catherine
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Brauer, Age
    Remm, Maido
    Tenson, Tanel
    Schulten, Klaus
    Vazquez-Laslop, Nora
    Mankin, Alexander S
    Macrolide antibiotics allosterically predispose the ribosome for translation arrest2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 27, p. 9804-9809Article in journal (Refereed)
    Abstract [en]

    Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosome stalling. However, here we show that macrolides arrest translation of the truncated ErmDL regulatory peptide when the nascent chain is only three amino acids and therefore is too short to be juxtaposed with the antibiotic. Biochemical probing and molecular dynamics simulations of erythromycin-bound ribosomes showed that the antibiotic in the tunnel allosterically alters the properties of the catalytic center, thereby predisposing the ribosome for halting translation of specific sequences. Our findings offer a new view on the role of small cofactors in the mechanism of translation arrest and reveal an allosteric link between the tunnel and the catalytic center of the ribosome.

  • 272. Starosta, Agata L.
    et al.
    Lassak, Jürgen
    Peil, Lauri
    Atkinson, Gemma C.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, Tartu, Estonia.
    Virumäe, Kai
    Tenson, Tanel
    Remme, Jaanus
    Jung, Kirsten
    Wilson, Daniel N.
    Translational stalling at polyproline stretches is modulated by the sequence context upstream of the stall site2014In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 42, no 16, p. 10711-10719Article in journal (Refereed)
    Abstract [en]

    The polymerization of amino acids into proteins occurs on ribosomes, with the rate influenced by the amino acids being polymerized. The imino acid proline is a poor donor and acceptor for peptide-bond formation, such that translational stalling occurs when three or more consecutive prolines (PPP) are encountered by the ribosome. In bacteria, stalling at PPP motifs is rescued by the elongation factor P (EF-P). Using SILAC mass spectrometry of Escherichia coli strains, we identified a subset of PPP-containing proteins for which the expression patterns remained unchanged or even appeared up-regulated in the absence of EF-P. Subsequent analysis using in vitro and in vivo reporter assays revealed that stalling at PPP motifs is influenced by the sequence context upstream of the stall site. Specifically, the presence of amino acids such as Cys and Thr preceding the stall site suppressed stalling at PPP motifs, whereas amino acids like Arg and His promoted stalling. In addition to providing fundamental insight into the mechanism of peptide-bond formation, our findings suggest how the sequence context of polyproline-containing proteins can be modulated to maximize the efficiency and yield of protein production.

  • 273.
    Stenmark, Stephan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lindgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    T-cell-dependent and independent protection against Francisella tularensisManuscript (preprint) (Other academic)
  • 274. Steptoe, A
    et al.
    Gylfe, Åsa
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Shamaei-Tousi, A
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Henderson, B
    Pathogen burden and cortisol profiles over the day2009In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 137, no 12, p. 1816-1824Article in journal (Refereed)
    Abstract [en]

    Hypothalamic-pituitary-adrenocortical (HPA) regulation in adults is influenced by early psychosocial adversity, but the role of infectious disease history is poorly understood. We studied the association between cumulative pathogen burden and cortisol profile over the day in a sample of 317 healthy men and women aged 51-72 years. Cumulative pathogen burden was defined as positive serostatus for Chlamydia pneumoniae, cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1). Salivary cortisol was sampled repeatedly over the day. The cortisol slope was defined as the decrease across the day and evening. Age, gender, grade of employment, body mass index, smoking status, self-rated health, cardiovascular medication, depressed mood and time of waking were included as covariates. The pathogen burden averaged 1.76 (S.D. = 0.92). The cortisol slope was inversely associated with pathogen burden after controlling for covariates. When individual pathogens were studied, only CMV was associated with flatter cortisol rhythms in isolation. We conclude that pathogen burden is independently associated with flatter cortisol slopes over the day, and may contribute to disturbed neuroendocrine regulation.

  • 275. Stoner, Marie C. D.
    et al.
    Dennis, Ann M.
    Hughes, James P.
    Eshleman, Susan H.
    Sivay, Marisa, V
    Hudelson, Sarah E.
    Grabowski, M. Kate
    Gomez-Olive, E. Xavier
    MacPhail, Catherine
    Piwowar-Manning, Estelle
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. INDEPTH Network, Accra, Ghana.
    Pettifor, Audrey
    Characteristics Associated With Human Immunodeficiency Virus Transmission Networks Involving Adolescent Girls and Young Women in Human Immunodeficiency Virus Prevention Trials Network 068 Study2019In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 46, no 5, p. E46-E49Article in journal (Refereed)
    Abstract [en]

    We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.

  • 276. Stoner, Marie C. D.
    et al.
    Edwards, Jessie K.
    Miller, William C.
    Aiello, Allison E.
    Halpern, Carolyn T.
    Julien, Aimee
    Rucinski, Katherine B.
    Selin, Amanda
    Twine, Rhian
    Hughes, James P.
    Wang, Jing
    Agyei, Yaw
    Gómez-Olivé, Francesc Xavier
    Wagner, Ryan G.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Laeyendecker, Oliver
    Macphail, Catherine
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; INDEPTH Network, Accra, Ghana.
    Pettifor, Audrey
    Does Partner Selection Mediate the Relationship Between School Attendance and HIV/Herpes Simplex Virus-2 Among Adolescent Girls and Young Women in South Africa: An Analysis of HIV Prevention Trials Network 068 Data2018In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 79, no 1, p. 20-27Article in journal (Refereed)
    Abstract [en]

    Objective: School attendance prevents HIV and herpes simplex virus-2 (HSV-2) in adolescent girls and young women, but the mechanisms to explain this relationship remain unclear. Our study assesses the extent to which characteristics of sex partners, partner age, and number mediate the relationship between attendance and risk of infection in adolescent girls and young women in South Africa.

    Design: We use longitudinal data from the HIV Prevention Trials Network 068 randomized controlled trial in rural South Africa, where girls were enrolled in early adolescence and followed in the main trial for more than 3 years. We examined older partners and the number of partners as possible mediators.

    Methods: We used the parametric g-formula to estimate 4-year risk differences for the effect of school attendance on the cumulative incidence of HIV/HSV-2 overall and the controlled direct effect (CDE) for mediation. We examined mediation separately and jointly for the mediators of interest.

    Results: We found that young women with high attendance in school had a lower cumulative incidence of HIV compared with those with low attendance (risk difference = -1.6%). Partner age difference (CDE = -1.2%) and the number of partners (CDE = -0.4%) mediated a large portion of this effect. In fact, when we accounted for the mediators jointly, the effect of schooling on HIV was almost removed, showing full mediation (CDE = -0.3%). The same patterns were observed for the relationship between school attendance and cumulative incidence of HSV-2 infection.

    Conclusion: Increasing school attendance reduces the risk of acquiring HIV and HSV-2. Our results indicate the importance of school attendance in reducing partner number and partner age difference in this relationship.

  • 277.
    Strand, Mårten
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Islam, Koushikul
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Öberg, Christopher T
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergström, Tomas
    Univ Gothenburg, Sahlgrenska Acad, Dept Virol, Gothenburg, Sweden.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus type 1 and 22012In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 11, p. 5735-5743Article in journal (Refereed)
    Abstract [en]

    Herpes simplex viruses (HSV-1 and HSV-2) are responsible for life-long latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tract. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity, and in some cases even mortality. Today, acyclovir is the standard therapy for management of HSV infections. However, the need for novel antiviral agents is apparent since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the anti-adenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid, (Benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, (Benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, Benzavir-2 had similar potency to acyclovir against both HSV types and it was active against clinical acyclovir-resistant HSV isolates.

  • 278. Sundling, Christopher
    et al.
    Ronnberg, Caroline
    Yman, Victor
    Asghar, Muhammad
    Jahnmatz, Peter
    Lakshmikanth, Tadepally
    Chen, Yang
    Mikes, Jaromir
    Forsell, Mattias N.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sonden, Klara
    Achour, Adnane
    Brodin, Petter
    Persson, Kristina E. M.
    Farnert, Anna
    B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets2019In: JCI Insight, ISSN 2379-3708, Vol. 4, no 9, article id e126492Article in journal (Refereed)
    Abstract [en]

    Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute Plasmodium fakiporum malaria for the first time or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that approximately 80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only approximately 40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared with individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay, with a half-life of approximately 300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary and secondary B cell responses during infection.

  • 279.
    Surowiec, Izabella
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Orikiiriza, Judy
    Lindquist, Elisabeth
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bonde, Mari
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Magambo, Jimmy
    Muhinda, Charles
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children2017In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, article id 358Article in journal (Refereed)
    Abstract [en]

    Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.

    Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).

    Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.

    Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.

  • 280.
    Surowiec, Izabella
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Orikiiriza, Judy
    Karlsson, Elisabeth
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Nelson, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bonde, Mari
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kyamanwa, Patrick
    Karenzi, Ben
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Normark, Johan
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. nfectious Diseases Institute, School of Medicine and Health Sciences, Makerere University, Uganda.
    Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria2015In: Open Forum Infectious Diseases, ISSN 2328-8957, Vol. 2, no 2Article in journal (Refereed)
    Abstract [en]

    Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.

  • 281.
    Svensson, Kerstin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Genetic genealogy and epidemiology of Francisella2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is about analyzing genetic differences among isolates of Francisella tularensis – the tularemia-causing bacterium. To elucidate how these bacterial isolates are related, and their geographical and genetic origins, I have developed typing assays for Francisella and used them to study the epidemiology of tularemia.

    Tularemia is an infectious disease of humans and other mammals found throughout the Northern Hemisphere. The severity of the disease depends on the type of F. tularensis causing the infection. In Sweden, as in other countries of Europe and Eurasia, tularemia is caused by F. tularensis subsp. holarctica, while other varieties of the bacterium occur in Middle Asia and North America. It is important to identify a tularemia infection promptly in order to initiate the correct antibiotic treatment. A rapid identification of the causative F. tularensis variety gives additional clinical information. In recent years, several genomes of various Francisella strains have been sequenced, and in this thesis, I have utilized these genomes to identify genetic markers.

    In studies reported in the first paper (I) appended to the thesis, we identified and analyzed insertion/deletion mutations (INDELs) inferred to have resulted from a sequence repeat-mediated excision mechanism. We found eight new Regions of Difference (RDs) among Francisella strains. Using RDs together with single nucleotide polymorphisms (SNPs), we were able to predict an evolutionary scenario for F. tularensis in which Francisella novicida was the oldest variety while F. tularensis subsp. holarctica was the youngest. We also found that all virulence-attenuated isolates analyzed had deletions at two specific genetic regions - denoted RD18 and RD19 – suggesting that repeat-mediated excision is a mechanism of attenuation in F. tularensis.

    In subsequent studies (presented in paper II), we developed a combined analysis of INDELs lacking flanking repeats and variable number of tandem repeats (VNTRs). Both markers could be assayed using the same analytical equipment. The inclusion of INDELs provided increased phylogenetic robustness compared with the use of VNTRs alone, while still maintaining a high level of genetic resolution.

    In analyses described in the next paper (III), we selected INDELs from paper (II) and discovered novel SNPs by DNA comparisons of multiple Francisella strains. Thirty-four phylogenetically informative genetic markers were included in a hierarchical real-time PCR array for rapid and robust characterization of Francisella. We successfully used the assay to genotype 14 F. tularensis isolates from tularemia patients and DNA in six clinical ulcer specimens.

    Finally, in paper (IV) we demonstrated a strategy to enhance epidemiological investigations of tularemia by combining GIS-mapping of disease-transmission place collected from patient interviews, with high-resolution genotyping of F. tularensis subsp. holarctica isolates recovered from tularemia patients. We found the geographic distributions of specific F. tularensis subsp. holarctica sub-populations to be highly localized during outbreaks (infections by some genotypes being restricted to areas as small as 2 km2), indicative of a landscape epidemiology of tularemia with distinct point sources of infection.

    In conclusion, the results acquired during the studies underlying this thesis contribute to our understanding of the genetic genealogy of tularemia at both global and local outbreak scales.

  • 282.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bäck, Erik
    Örebro universitet.
    Berglund, Lennart
    Eliasson, Henrik
    Granberg, M
    Karlsson, Lena
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, Mats
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    A high-resolution landscape epidemiology of tularemia exposed by genetic analysis of the causative agent isolated from infected humansManuscript (Other academic)
  • 283.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bäck, Erik
    Örebro Universitetssjukhus.
    Eliasson, Henrik
    Örebro Universitetssjukhus.
    Berglund, Lennart
    Granberg, Malin
    Karlsson, Linda
    Swedish Defense Research Agency, Umea, Sweden.
    Larsson, Pär
    Swedish Defense Research Agency, Umea, Sweden.
    Forsman, Mats
    Swedish Defense Research Agency, Umea, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Landscape epidemiology of tularemia outbreaks in Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 12, p. 1937-1947Article in journal (Refereed)
    Abstract [en]

    Summer outbreaks of tularemia that occurred from 1995 through 2005 in 2 locations in Sweden affected 441 persons. We performed an epidemiologic investigation of these outbreaks using a novel strategy, involving high-resolution genotyping of Francisella tularensis isolates obtained from 136 patients (using 18 genetic markers developed from 6 F. tularensis genome sequences) and interviews with the patients. Strong spatial associations were found between F. tularensis subpopulations and the places of disease transmission; infection by some subpopulations occurred within areas as small as 2 km(2), indicating unidentified environmental point sources of tularemia. In both locations, disease clusters were associated with recreational areas beside water, and genetic subpopulations were present throughout the tularemia season and persisted over years. High-resolution genotyping in combination with patients' statements about geographic places of disease transmission provided valuable indications of likely sources of infection and the causal genotypes during these tularemia outbreaks.

  • 284.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Division of CBRN Defense and Security, Swedish Defense Research Agency, Umeå, Sweden .
    Granberg, Malin
    Karlsson, Linda
    Neubauerova, Vera
    Forsman, Mats
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Division of CBRN Defense and Security, Swedish Defense Research Agency, Umeå, Sweden .
    A real-time PCR array for hierarchical identification of Francisella isolates2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 12, article id e8360Article in journal (Refereed)
    Abstract [en]

    A robust, rapid and flexible real-time PCR assay for hierarchical genetic typing of clinical and environmental isolates of Francisella is presented. Typing markers were found by multiple genome and gene comparisons, from which 23 canonical single nucleotide polymorphisms (canSNPs) and 11 canonical insertion-deletion mutations (canINDELs) were selected to provide phylogenetic guidelines for classification from genus to isolate level. The specificity of the developed assay, which uses 68 wells of a 96-well real-time PCR format with a detection limit of 100 pg DNA, was assessed using 62 Francisella isolates of diverse genetic and geographical origins. It was then successfully used for typing 14 F. tularensis subsp. holarctica isolates obtained from tularemia patients in Sweden in 2008 and five more genetically diverse Francisella isolates of global origins. When applied to human ulcer specimens for direct pathogen detection the results were incomplete due to scarcity of DNA, but sufficient markers were identified to detect fine-resolution differences among F. tularensis subsp. holarctica isolates causing infection in the patients. In contrast to other real-time PCR assays for Francisella, which are typically designed for specific detection of a species, subspecies, or strain, this type of assay can be easily tailored to provide appropriate phylogenetic and/or geographical resolution to meet the objectives of the analysis.

  • 285.
    Tafazoli, Farideh
    et al.
    Division of Medical Microbiology, Department of Health and Environment, Linköping University, Linköping, Sweden.
    Holmström, Anna
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Forsberg, Åke
    Department of Microbiology, National Defence Research Establishment, Umeå, Sweden.
    Magnusson, Karl-Eric
    Division of Medical Microbiology, Department of Health and Environment, Linköping University, Linköping, Sweden.
    Apically exposed, tight junction-associated beta1-integrins allow binding and YopE-mediated perturbation of epithelial barriers by wild-type Yersinia bacteria2000In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 68, no 9, p. 5335-5343Article in journal (Refereed)
    Abstract [en]

    Using polarized epithelial cells, primarily MDCK-1, we assessed the mode of binding and effects on epithelial cell structure and permeability of Yersinia pseudotuberculosis yadA-deficient mutants. Initially, all bacteria except the invasin-deficient (inv) mutant adhered apically to the tight junction areas. These contact points of adjacent cells displayed beta1-integrins together with tight junction-associated ZO-1 and occludin proteins. Indeed, beta1-integrin expression was maximal in the tight junction area and then gradually decreased along the basolateral membranes. Wild-type bacteria also opened gradually the tight junction to paracellular permeation of different-sized markers, viz., 20-, 40-, and 70-kDa dextrans and 45-kDa ovalbumin, as well as to their own translocation between adjacent cells in intimate contact with beta1-integrins. The effects on the epithelial cells and their barrier properties could primarily be attributed to expression of the Yersinia outer membrane protein YopE, as the yopE mutant bound but caused no cytotoxicity. Moreover, the apical structure of filamentous actin (F-actin) was disturbed and tight junction-associated proteins (ZO-1 and occludin) were dispersed along the basolateral membranes. It is concluded that the Yersinia bacteria attach to beta1-integrins at tight junctions. Via this localized injection of YopE, they perturb the F-actin structure and distribution of proteins forming and regulating tight junctions. Thereby they promote paracellular translocation of bacteria and soluble compounds.

  • 286. Takata, Tohru
    et al.
    Miyazaki, Motoyasu
    Futo, Maki
    Hara, Shuji
    Shiotsuka, Shouichi
    Kamimura, Hidetoshi
    Yoshimura, Hisae
    Matsunaga, Akira
    Nishida, Takeshi
    Ishikura, Hiroyasu
    Ishikawa, Takahiko
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Tamura, Kazuo
    Tsuji, Brian T.
    Presence of both heterogeneous vancomycin-intermediate resistance and beta-lactam antibiotic-induced vancomycin resistance phenotypes is associated with the outcome in methicillin-resistant Staphylococcus aureus bloodstream infection2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 3, p. 203-212Article in journal (Refereed)
    Abstract [en]

    Background: Although the individual expression of heterogeneous vancomycin-intermediate resistance (hVISA) and beta-lactam antibiotic-induced vancomycin resistance (BIVR) phenotypes has been associated with treatment failure and recurrence in methicillin-resistant Staphylococcus aureus (MRSA) infections, the effect of the co-expression of these phenotypic profiles on clinical outcome has not been fully elucidated. The aim of this study was to determine the impact of the combination of hVISA and BIVR phenotypes on the clinical outcome in MRSA bacteremia. Methods: One hundred and sixty-two MRSA blood isolates from a 21-y period, 1987-2007, were randomly selected. Screening for hVISA was done by the macromethod Etest and confirmed by population analysis profiles. BIVR was identified using Mu3 agar containing 4 mu g/ml of vancomycin. Results: Thirty (18.5%) and 39 (24.1%) of the 162 MRSA blood isolates were positive for the hVISA and BIVR phenotypes, respectively. Eighteen (11.1%) isolates possessed both hVISA and BIVR phenotypes (hVISA(+)/BIVR(+)). In a subset of patients who received initial treatment with glycopeptides, only the patients whose isolates were hVISA(+)/BIVR(+) displayed a significantly higher mortality rate in comparison to those with non-hVISA(+)/BIVR(+) (80.0% vs 31.3%, p = 0.004). The presence of both hVISA and BIVR phenotypes was a predictor of mortality using a logistic regression analysis (p = 0.025). Conclusions: The combined phenotype of hVISA and BIVR was associated with a higher probability of mortality in patients with MRSA bacteremia. Further prospective studies are warranted to delineate the clinical significance of the combined phenotype of hVISA and BIVR.

  • 287. Talagrand-Reboul, Emilie
    et al.
    Boyer, Pierre H.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Vial, Laurence
    Boulanger, Nathalie
    Relapsing Fevers: Neglected Tick-Borne Diseases2018In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, article id 98Article, review/survey (Refereed)
    Abstract [en]

    Relapsing fever still remains a neglected disease and little is known on its reservoir, tick vector and physiopathology in the vertebrate host. The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family which also contain Lyme disease spirochaetes. They are mainly transmitted by Ornithodoros soft ticks, but some species are vectored by ixodid ticks. Traditionally a Borrelia species is associated with a specific vector in a particular geographical area. However, new species are regularly described, and taxonomical uncertainties deserve further investigations to better understand Borrelia vector/host adaptation. The medical importance of Borrelia miyamotoi, transmitted by Ixodes spp., has recently spawned new interest in this bacterial group. In this review, recent data on tick-host-pathogen interactions for tick-borne relapsing fevers is presented, with special focus on B. miyamotoi.

  • 288. Tissera, Hasitha
    et al.
    Rathore, Abhay P. S.
    Leong, Wei Yee
    Pike, Brian L.
    Warkentien, Tyler E.
    Farouk, Farouk S.
    Syenina, Ayesa
    Ooi, Eng Eong
    Gubler, Duane J.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    John, Ashley L. St.
    Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients2017In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 216, no 9, p. 1112-1121Article in journal (Refereed)
    Abstract [en]

    Background. Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Methods. Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. Results. An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. Conclusions. These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients.

  • 289.
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Management of complicated skin and skin structure infections: a call for infectious disease specialists2018In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, no 2, p. 117-118Article in journal (Other academic)
  • 290. Tükenmez, Hasan
    et al.
    Edström, Isabel
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Ummanni, Ramesh
    Fick, Stina Berglund
    Sundin, Charlotta
    Elofsson, Mikael
    Larsson, Christer
    Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 26Article in journal (Refereed)
    Abstract [en]

    High-throughput screening facilities do not generally support biosafety level 3 organisms such as Mycobacterium tuberculosis. To discover not only antibacterials, but also virulence inhibitors with either bacterial or host cell targets, an assay monitoring lung fibroblast survival upon infection was developed and optimized for 384-plate format and robotic liquid handling. By using Mycobacterium marinum as surrogate organism, 28,000 compounds were screened at biosafety level 2 classification, resulting in 49 primary hits. Exclusion of substances with unfavourable properties and known antimicrobials resulted in 11 validated hits of which 7 had virulence inhibiting properties and one had bactericidal effect also in wild type Mycobacterium tuberculosis. This strategy to discover virulence inhibitors using a model organism in high-throughput screening can be a valuable tool for other researchers working on drug discovery against tuberculosis and other biosafety level 3 infectious agents.

  • 291.
    Urban, Constantin F
    et al.
    Department for Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
    Ermert, David
    Schmid, Monika
    Abu-Abed, Ulrike
    Goosmann, Christian
    Nacken, Wolfgang
    Brinkmann, Volker
    Jungblut, Peter R
    Zychlinsky, Arturo
    Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans2009In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 5, no 10, article id e1000639Article in journal (Refereed)
    Abstract [en]

    Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins and the release of Neutrophil Extracellular Traps (NETs). NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.

  • 292.
    Valeru, Soni Priya
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Rompikuntal, Pramod Kumar
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ishikawa, Takahiko
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Vaitkevicius, Karolis
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sjöling, Åsa
    Dolganov, Nadia
    Zhu, Jun
    Schoolnik, Gary
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Role of melanin pigment in expression of Vibrio cholerae virulence factors2009In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 77, no 3, p. 935-942Article in journal (Refereed)
    Abstract [en]

    We identified the mutated gene locus in a pigment-overproducing Vibrio cholerae mutant of strain A1552. The deduced gene product is suggested to be an oxidoreductase based on partial homology to putative homogentisate 1,2-dioxygenase in Pseudomonas aeruginosa and Mesorhizobium loti, and we propose that the gene VC1345 in the V. cholerae genome be denoted hmgA in accordance with the nomenclature for other species. The hmgA:: mini-Tn5 mutant showed a nonpigmented phenotype after complementation with a plasmid clone carrying the WT hmgA(+) locus. Microarray transcription analysis revealed that expression of hmgA and the neighboring genes encoding a postulated two-component sensor system was growth phase dependent. Results from quantitative reverse transcription-PCR analysis showed that hmgA operon expression was reduced in the rpoS mutant, but pigment production by the WT V. cholerae or the hmgA mutant was not detectably influenced by the stationary-phase regulator RpoS. The pigmented mutant showed increased UV resistance in comparison with the WT strain. Interestingly, the pigment-producing mutant expressed more toxin-coregulated pilus and cholera toxin than WT V. cholerae. Moreover, the hmgA mutant showed a fivefold increase in the ability to colonize the intestines of infant mice. A possible mechanism by which pigment production might cause induction of the ToxR regulon due to generation of hydrogen peroxide was supported by results from tests showing that externally supplied H2O2 led to higher TcpA levels. Taken together, our findings suggest that melanin pigment formation may play a role in V. cholerae virulence factor expression.

  • 293. van Schaarenburg, Rosanne A.
    et al.
    Schejbel, Lone
    Truedsson, Lennart
    Topaloglu, Rezan
    Al-Mayouf, Sulaiman M.
    Riordan, Andrew
    Simon, Anna
    Kallel-Sellami, Maryam
    Arkwright, Peter D.
    Ahlin, Anders
    Hagelberg, Stefan
    Nielsen, Susan
    Shayesteh, Alexander
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Morales, Adelaida
    Tam, Schuman
    Genel, Ferah
    Berg, Stefan
    Ketel, Arnoldus G.
    van den Berg, J. Merlijn
    Kuijpers, Taco W.
    Olsson, Richard F.
    Huizinga, Tom W. J.
    Lankester, Arjan C.
    Trouw, Leendert A.
    Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency2015In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 62, p. 39-44Article in journal (Refereed)
    Abstract [en]

    Objective: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease.

    Methods: We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published.

    Results: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient individuals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages.

    Conclusion: Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance; with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.

  • 294. Vanha-aho, Leena-Maija
    et al.
    Anderl, Ines
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    Vesala, Laura
    Hultmark, Dan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Laboratory of Genetic Immunology, BioMediTech, University of Tampere, Tampere, Finland.
    Valanne, Susanna
    Rämet, Mika
    Edin expression in the fat body is required in the defense against parasitic wasps in Drosophila melanogaster2015In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 11, no 5, article id e1004895Article in journal (Refereed)
    Abstract [en]

    The cellular immune response against parasitoid wasps in Drosophila involves the activation, mobilization, proliferation and differentiation of different blood cell types. Here, we have assessed the role of Edin (elevated during infection) in the immune response against the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster larvae. The expression of edin was induced within hours after a wasp infection in larval fat bodies. Using tissue-specific RNAi, we show that Edin is an important determinant of the encapsulation response. Although edin expression in the fat body was required for the larvae to mount a normal encapsulation response, it was dispensable in hemocytes. Edin expression in the fat body was not required for lamellocyte differentiation, but it was needed for the increase in plasmatocyte numbers and for the release of sessile hemocytes into the hemolymph. We conclude that edin expression in the fat body affects the outcome of a wasp infection by regulating the increase of plasmatocyte numbers and the mobilization of sessile hemocytes in Drosophila larvae.

  • 295. Vesikari, Timo
    et al.
    Richardus, Jan Hendrik
    Berglund, Johan
    Korhonen, Tiina
    Flodmark, Carl-Erik
    Lindstrand, Ann
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bambure, Vinod
    Caplanusi, Adrian
    Dieussaert, Ilse
    Roy-Ghanta, Sumita
    Vaughn, David W.
    Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine Two Open-label, Randomized Trials2015In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 34, no 7, p. 774-782Article in journal (Refereed)
    Abstract [en]

    Background: During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1) pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1) pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1) pdm09 vaccine. Methods: Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1) pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1) pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. Results: At day 0, >93.9% of all children had HI titers >= 1:40 for the A(H1N1) pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1) pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. Conclusion: AS03-adjuvanted A(H1N1) pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1) pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03adjuvanted A(H1N1) pdm09 vaccine.

  • 296.
    Vesterlund, Agnes
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Complications related to central venous catheters at Norrland University hospital (Nus), 2016-20172018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 297. Vogt, Alexander
    et al.
    Scull, Margaret A
    Friling, Tamar
    Horwitz, Joshua A
    Donovan, Bridget M
    Dorner, Marcus
    Gerold, Gisa
    Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
    Labitt, Rachael N
    Rice, Charles M
    Ploss, Alexander
    Recapitulation of the hepatitis C virus life-cycle in engineered murine cell lines2013In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 444, no 1-2, p. 1-11Article in journal (Refereed)
    Abstract [en]

    Hepatitis C virus (HCV) remains a major medical problem. In-depth study of HCV pathogenesis and immune responses is hampered by the lack of suitable small animal models. The narrow host range of HCV remains incompletely understood. We demonstrate that the entire HCV life-cycle can be recapitulated in mouse cells. We show that antiviral signaling interferes with HCV RNA replication in mouse cells. We were able to infect mouse cells expressing human CD81 and occludin (OCLN)-the minimal set of entry factor factors required for HCV uptake into mouse cells. Infected mouse cells sustain HCV RNA replication in the presence of miR122 and release infectious particles when mouse apoE is supplied. Our data demonstrate that the barriers of HCV interspecies transmission can be overcome by engineering a suitable cellular environment and provide a blue-print towards constructing a small animal model for HCV infection.

  • 298.
    Vågberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Kumlin, Urban
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Humoral immune response to influenza vaccine in natalizumab-treated MS patients2012In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 34, no 7, p. 730-733Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Natalizumab is a drug with documented efficacy in relapsing?remitting multiple sclerosis (RRMS). The mechanism of action of natalizumab has immunosuppressive properties and it is not yet investigated if treatment with natalizumab affects the immunological response to vaccination. This study aims to investigate the humoral immune response to influenza vaccine while undergoing treatment with natalizumab.

    METHODS: A cohort of 17 RRMS patients treated with natalizumab and 10 healthy controls received trivalent influenza A/B vaccine. Influenza-specific immunoglobulin G (IgG) levels were determined at baseline and after 4, 8, and 12 weeks.

    RESULTS: Both groups experienced a significant increase in anti-influenza B IgG after the vaccination. Both groups also experienced a smaller increase in anti-influenza A IgG, but this was only significant for the natalizumab group. The IgG titers compared between the groups did not differ significantly at any of the time points.

    DISCUSSION: These results indicate that vaccination against influenza in patients treated with natalizumab yields a humoral immune response comparable to that achieved in healthy individuals.

  • 299. Wallensten, A
    et al.
    Munster, VJ
    Fouchier, RAM
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Research Institute of Zoonotic Ecology and Epidemiology., Kalmar, Sweden.
    Avian Influenza A virus in ducks migrating through Sweden2004In: Options for the control of influenza V / [ed] Kawaoka, Y, Amsterdam: Elsevier, 2004, p. 771-772Conference paper (Refereed)
    Abstract [en]

    In order to investigate the prevalence and ecology of the Avian Influenza A virus (AIV) in western Palearctic wild birds, migrating ducks, mainly Mallards (Anas platyrhynchos), have been caught in a funnel trap at the Ottenby Bird Observatory on the Swedish Island Oland. After banding and collection of biometrical data, every individual was sampled for AIV Since the fall of 2002, more than 3200 samples from 1900 birds have been collected showing a prevalence of AIV of 12%. Several subtypes have been found, including the low pathogenic H5N2. Some ducks are re-caught both during fall and spring migration, and the recruiting and wintering areas of the birds are known enabling us to draw conclusions about the geographical and reservoir distribution of AIV. (C) 2003 Elsevier B.V All rights reserved.

  • 300.
    Wang, He
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Avican, Kemal
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Erttmann, Saskia F.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Nuss, Aaron M.
    Dersch, Petra
    Fällman, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Edgren, Tomas
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Increased plasmid copy number is essential for Yersinia T3SS function and virulence2016In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 353, no 6298, p. 492-495Article in journal (Refereed)
    Abstract [en]

    Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacterium Yersinia uses a type III secretion system (T3SS) encoded by a 70-kilobase, low-copy, IncFII-class virulence plasmid. We report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copy number during infection. We found that an increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we observed direct, tight coupling between plasmid replication and T3SS function. This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria.

34567 251 - 300 of 328
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf