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Olofsson, Annelie
Publications (10 of 12) Show all publications
Javadi, A., Söderholm, N., Olofsson, A., Flärdh, K. & Sandblad, L. (2019). Assembly mechanisms of the bacterial cytoskeletal protein FilP. Life Science Alliance, 2(3), Article ID e201800290.
Open this publication in new window or tab >>Assembly mechanisms of the bacterial cytoskeletal protein FilP
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2019 (English)In: Life Science Alliance, ISSN 2575-1077, Vol. 2, no 3, article id e201800290Article in journal (Refereed) Published
Abstract [en]

Despite low-sequence homology, the intermediate filament (IF)–like protein FilP from Streptomyces coelicolor displays structural and biochemical similarities to the metazoan nuclear IF lamin. FilP, like IF proteins, is composed of central coiled-coil domains interrupted by short linkers and flanked by head and tail domains. FilP polymerizes into repetitive filament bundles with paracrystalline properties. However, the cations Na+ and K+ are found to induce the formation of a FilP hexagonal meshwork with the same 60-nm repetitive unit as the filaments. Studies of polymerization kinetics, in combination with EM techniques, enabled visualization of the basic building block — a transiently soluble rod-shaped FilP molecule—and its assembly into protofilaments and filament bundles. Cryoelectron tomography provided a 3D view of the FilP bundle structure and an original assembly model of an IF-like protein of prokaryotic origin, thereby enabling a comparison with the assembly of metazoan IF.

Place, publisher, year, edition, pages
Life Science Alliance, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-161722 (URN)10.26508/lsa.201800290 (DOI)000473222200011 ()31243049 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationThe Kempe FoundationsSwedish Research Council, 2011-05198
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-10-14Bibliographically approved
Rajan, A., Persson, B. D., Frängsmyr, L., Olofsson, A., Sandblad, L., Heino, J., . . . Arnberg, N. (2018). Enteric species F human adenoviruses use laminin-binding integrins as co-receptors for infection of Ht-29 cells. Scientific Reports, 8(1), Article ID 10019.
Open this publication in new window or tab >>Enteric species F human adenoviruses use laminin-binding integrins as co-receptors for infection of Ht-29 cells
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 10019Article in journal (Refereed) Published
Abstract [en]

The enteric species F human adenovirus types 40 and 41 (HAdV-40 and -41) are the third most common cause of infantile gastroenteritis in the world. Knowledge about HAdV-40 and -41 cellular infection is assumed to be fundamentally different from that of other HAdVs since HAdV-40 and -41 penton bases lack the αV-integrin-interacting RGD motif. This motif is used by other HAdVs mainly for internalization and endosomal escape. We hypothesised that the penton bases of HAdV-40 and -41 interact with integrins independently of the RGD motif. HAdV-41 transduction of a library of rodent cells expressing specific human integrin subunits pointed to the use of laminin-binding α2-, α3- and α6-containing integrins as well as other integrins as candidate co-receptors. Specific laminins prevented internalisation and infection, and recombinant, soluble HAdV-41 penton base proteins prevented infection of human intestinal HT-29 cells. Surface plasmon resonance analysis demonstrated that HAdV-40 and -41 penton base proteins bind to α6-containing integrins with an affinity similar to that of previously characterised penton base:integrin interactions. With these results, we propose that laminin-binding integrins are co-receptors for HAdV-40 and -41.

Place, publisher, year, edition, pages
Springer Nature, 2018
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-146978 (URN)10.1038/s41598-018-28255-7 (DOI)000437097000036 ()29968781 (PubMedID)2-s2.0-85049507353 (Scopus ID)
Note

Originally included in thesis in manuscript form.

Available from: 2018-04-24 Created: 2018-04-24 Last updated: 2018-08-29Bibliographically approved
Turkina, M. V., Olofsson, A., Magnusson, K.-E., Arnqvist, A. & Vikstrom, E. (2015). Helicobacter pylori vesicles carrying CagA localize in the vicinity of cell-cell contacts and induce histone H1 binding to ATP in epithelial cells. FEMS Microbiology Letters, 362(11), Article ID fnv076.
Open this publication in new window or tab >>Helicobacter pylori vesicles carrying CagA localize in the vicinity of cell-cell contacts and induce histone H1 binding to ATP in epithelial cells
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2015 (English)In: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 362, no 11, article id fnv076Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori produces outer membrane vesicles (OMV), delivering bacterial substances including the oncogenic cytotoxin-associated CagA protein to their surroundings. We investigated the effects of H. pylori OMV carrying CagA (OMV-CagA) on cell junctions and ATP-binding proteome of epithelial monolayers, using proteomics, mass spectrometry and imaging. OMV-CagA localized in close vicinity of ZO-1 tight junction protein and induced histone H1 binding to ATP. We suggest the expression of novel events in the interactions between H. pylori OMV and epithelia, which may have an influence on host gene transcription and lead to different outcomes of an infection and development of cancer.

Keywords
Helicobacter pylori, outer membrane vesicles, CagA, ATP-proteome, histone H1, epithelial cell-cell junctions
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-106572 (URN)10.1093/femsle/fnv076 (DOI)000356890900007 ()
Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2018-06-07Bibliographically approved
Åberg, A., Gideonsson, P., Vallström, A., Olofsson, A., Öhman, C., Rakhimova, L., . . . Arnqvist, A. (2014). A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism. PLoS Pathogens, 10(7), Article ID e1004234.
Open this publication in new window or tab >>A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
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2014 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 7, article id e1004234Article in journal (Refereed) Published
Abstract [en]

During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors.

National Category
Physiology Physical Chemistry
Identifiers
urn:nbn:se:umu:diva-91641 (URN)10.1371/journal.ppat.1004234 (DOI)000340551000026 ()24991812 (PubMedID)
Available from: 2014-08-13 Created: 2014-08-13 Last updated: 2018-06-07Bibliographically approved
Olofsson, A., Nygård Skalman, L., Obi, I., Lundmark, R. & Arnqvist, A. (2014). Uptake of Helicobacter pylori vesicles is facilitated by clathrin-dependent and clathrin-independent endocytic pathways. mBio, 5(3), e00979-14
Open this publication in new window or tab >>Uptake of Helicobacter pylori vesicles is facilitated by clathrin-dependent and clathrin-independent endocytic pathways
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2014 (English)In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 5, no 3, p. e00979-14-Article in journal (Refereed) Published
Abstract [en]

UNLABELLED: Bacteria shed a diverse set of outer membrane vesicles that function as transport vehicles to deliver effector molecules and virulence factors to host cells. Helicobacter pylori is a gastric pathogen that infects half of the world's population, and in some individuals the infection progresses into peptic ulcer disease or gastric cancer. Here we report that intact vesicles from H. pylori are internalized by clathrin-dependent endocytosis and further dynamin-dependent processes, as well as in a cholesterol-sensitive manner. We analyzed the uptake of H. pylori vesicles by gastric epithelial cells using a method that we refer to as quantification of internalized substances (qIS). The qIS assay is based on a near-infrared dye with a cleavable linker that enables the specific quantification of internalized substances after exposure to reducing conditions. Both chemical inhibition and RNA interference in combination with the qIS assay showed that H. pylori vesicles enter gastric epithelial cells via both clathrin-mediated endocytosis and additional endocytic processes that are dependent on dynamin. Confocal microscopy revealed that H. pylori vesicles colocalized with clathrin and dynamin II and with markers of subsequent endosomal and lysosomal trafficking. Interestingly, however, knockdown of components required for caveolae had no significant effect on internalization and knockdown of components required for clathrin-independent carrier (CLIC) endocytosis increased internalization of H. pylori vesicles. Furthermore, uptake of vesicles by both clathrin-dependent and -independent pathways was sensitive to depletion, but not sequestering, of cholesterol in the host cell membrane suggesting that membrane fluidity influences the efficiency of H. pylori vesicle uptake.

IMPORTANCE: Bacterial vesicles act as long-distance tools to deliver toxins and effector molecules to host cells. Vesicles can cause a variety of host cell responses via cell surface-induced cell signaling or internalization. Vesicles of diverse bacterial species enter host cells via different endocytic pathways or via membrane fusion. With the combination of a fluorescence-based quantification assay that quantifies internalized vesicles in a large number of cells and either chemical inhibition or RNA interference, we show that clathrin-mediated endocytosis is the major pathway for uptake of Helicobacter pylori vesicles and that lipid microdomains of the host cell membrane affect uptake of vesicles via clathrin-independent pathways. Our results provide important insights about membrane fluidity and its important role in the complex process that directs the H. pylori vesicle to a specific endocytic pathway. Understanding the mechanisms that operate in vesicle-host interactions is important to fully recognize the impact of vesicles in pathogenesis.

National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-90953 (URN)10.1128/mBio.00979-14 (DOI)000338875900050 ()24846379 (PubMedID)
Available from: 2014-07-04 Created: 2014-07-04 Last updated: 2018-06-07Bibliographically approved
Olofsson, A. (2013). Helicobacter pylori outer membrane vesicles and the host-pathogen interaction. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Helicobacter pylori outer membrane vesicles and the host-pathogen interaction
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Helicobacter pylori membranvesiklar och interaktioner med värdcellen
Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013. p. 56
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1559
Keywords
H. pylori, outer membrane vesicles, 2D 31P, 1H COSY NMR, phospholipids, OMV proteome, adherence, endocytosis, CagA, OMV-host cell responses, yttermembran vesiklar
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-68744 (URN)978-91-7459-578-9 (ISBN)
Public defence
2013-05-17, KB3B1, KBC-huset, Umeå universitet, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2013-04-26 Created: 2013-04-24 Last updated: 2018-06-08Bibliographically approved
Olofsson, A., Vallström, A., Petzold, K., Tegtmeyer, N., Schleucher, J., Carlsson, S., . . . Arnqvist, A. (2010). Biochemical and functional characterization of Helicobacter pylori vesicles. Molecular Microbiology, 77(6), 1539-1555
Open this publication in new window or tab >>Biochemical and functional characterization of Helicobacter pylori vesicles
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2010 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 77, no 6, p. 1539-1555Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor to the vigor of infection and resulting virulence. H. pylori adheres primarily via binding of BabA adhesins to ABO/Lewis b (Leb) blood group antigens and the binding of SabA adhesins to sialyl-Lewis x/a (sLex/a) antigens. Similar to most Gram-negative bacteria, H. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often include virulence-associated factors. Here we biochemically characterized highly purified H. pylori vesicles. Major protein and phospholipid components associated with the vesicles were identified with mass spectroscopy and NMR. A subset of virulence factors present was confirmed by immunoblots. Additional functional and biochemical analysis focused on the vesicle BabA and SabA adhesins and their respective interactions to human gastric epithelium. Vesicles exhibit heterogeneity in their protein composition, which were specifically studied in respect to the BabA adhesin. We also demonstrate that the oncoprotein, CagA, is associated with the surface of H. pylori vesicles. Thus, we have explored mechanisms for intimate H. pylori vesicle-host interactions and found that the vesicles carry effector-promoting properties that are important to disease development.

Place, publisher, year, edition, pages
Wiley, 2010
Identifiers
urn:nbn:se:umu:diva-35586 (URN)10.1111/j.1365-2958.2010.07307.x (DOI)000281831400018 ()20659286 (PubMedID)
Available from: 2010-08-24 Created: 2010-08-24 Last updated: 2018-06-08Bibliographically approved
Petzold, K., Olofsson, A., Arnqvist, A., Gröbner, G. & Jürgen, S. (2009). Semiconstant-Time P,H-COSY NMR: Analysis of Complex Mixtures of Phospholipids Originating from Helicobacter pylori. Journal of the American Chemical Society, 131(40), 14150-1
Open this publication in new window or tab >>Semiconstant-Time P,H-COSY NMR: Analysis of Complex Mixtures of Phospholipids Originating from Helicobacter pylori
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2009 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 40, p. 14150-1Article in journal (Refereed) Published
Abstract [en]

Lipids play a central role in numerous biological events, ranging from normal physiological processes to host−pathogen interactions. The proposed semiconstant-time 31P,1H−COSY NMR experiment provides identification of known and structural characterization of unknown phospholipids in complex membrane extracts with high sensitivity, based on the combination of their 1H and 31P chemical shifts and coupling patterns. Furthermore, the spectra allow quantification of phospholipid composition. Analysis of the phospholipid composition of Helicobacter pylori, the causative agent of peptic ulcer disease, showed the presence of uncommon phospholipids. This novel NMR approach allows the study of changes in membrane composition in response to biological stimuli and opens up the possibility of identifying soluble phosphorus species in a number of research fields.

Place, publisher, year, edition, pages
ACS Publications ASAP, 2009
Identifiers
urn:nbn:se:umu:diva-26035 (URN)10.1021/ja905282h (DOI)
Note
Publication Date (Web): September 17, 2009Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2018-06-08Bibliographically approved
Olofsson, A., Bäckström, A., Petzold, K., Gröbner, G., Wai, S., Carlsson, S., . . . Arnqvist, A. (Eds.). (2007). Helicobacter pylori outer membrane vesicles and properties for intimate host interactions. BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
Open this publication in new window or tab >>Helicobacter pylori outer membrane vesicles and properties for intimate host interactions
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2007 (English)Conference proceedings (editor) (Refereed)
Place, publisher, year, edition, pages
BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND, 2007
Identifiers
urn:nbn:se:umu:diva-11601 (URN)
Note
Meeting Abstract ZOONOSES AND PUBLIC HEALTH Volume: 54 Pages: 93-94 Supplement: Suppl. 1 Published: 2007Available from: 2009-01-22 Created: 2009-01-22 Last updated: 2018-06-09Bibliographically approved
Olofsson, A., Vallström, A., Petzold, K., Schleucher, J., Carlsson, S., Haas, R., . . . Arnqvist, A. Characterization of Helicobacter pylori vesicles and their cognate properties for intimate host interactions.
Open this publication in new window or tab >>Characterization of Helicobacter pylori vesicles and their cognate properties for intimate host interactions
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(English)Manuscript (preprint) (Other academic)
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-25737 (URN)
Available from: 2009-09-01 Created: 2009-09-01 Last updated: 2018-06-08Bibliographically approved
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