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Wai, Sun Nyunt
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Publications (10 of 93) Show all publications
Taheri, N., Fällman, M., Wai, S. N. & Fahlgren, A. (2019). Accumulation of virulence-associated proteins in Campylobacter jejuni Outer Membrane Vesicles at human body temperature. Journal of Proteomics, 195, 33-40
Open this publication in new window or tab >>Accumulation of virulence-associated proteins in Campylobacter jejuni Outer Membrane Vesicles at human body temperature
2019 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 195, p. 33-40Article in journal (Refereed) Published
Abstract [en]

Campylobacter jejuni is the major cause of bacterial gastroenteritis in humans. In contrast, colonization in avian hosts is asymptomatic. Body temperature differs between human (37 °C) and avian (42 °C) hosts, and bacterial growth in 37 °C is therefore a potential cue for higher virulence properties during human infection. The proteome of the bacteria was previously shown to be altered by temperature. Here we investigated whether temperature has an effect on the C. jejuni outer membrane vesicle (OMV) proteome, as OMVs are considered to be bacterial vehicles for protein delivery and might play a role during infection. OMVs isolated from C. jejuni strain 81-176 grown at 37 °C and 42 °C were analyzed by LC-ESI-MS/MS. 181 proteins were detected in both sample groups, one protein was exclusively present, and three were absent in OMVs from 37 °C. Of the 181 proteins, 59 were differentially expressed; 30 proteins were detected with higher abundance, and 29 proteins with lower abundance at 37 °C. Among the more highly abundant proteins, significantly more proteins were predicted to be associated with virulence. These data show that temperature has an impact on the property of the OMVs, and this might affect the outcome of colonization/infection by C. jejuni in different hosts.

Keywords
Campylobacter jejuni, OMVs, Proteomics, Temperature
National Category
Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-155499 (URN)10.1016/j.jprot.2019.01.005 (DOI)000459366000004 ()30641234 (PubMedID)
Available from: 2019-01-18 Created: 2019-01-18 Last updated: 2019-04-16Bibliographically approved
Ahmad, I., Karah, N., Nadeem, A., Wai, S. N. & Uhlin, B. E. (2019). Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates. PLoS ONE, 14(1), Article ID e0210082.
Open this publication in new window or tab >>Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0210082Article in journal (Refereed) Published
Abstract [en]

Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.

Place, publisher, year, edition, pages
Public Library Science, 2019
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-155634 (URN)10.1371/journal.pone.0210082 (DOI)000454952800043 ()30608966 (PubMedID)
Funder
Swedish Research Council, 2015-03007Swedish Research Council, 2015-06824Swedish Research Council, 2016-06598Swedish Research Council, 349-2007-8673Swedish Research Council, 829-2006-7431The Kempe Foundations, JCK-1527The Kempe Foundations, JCK-1724
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2019-01-25Bibliographically approved
Cavanagh, J. P., Pain, M., Askarian, F., Bruun, J.-A., Urbarova, I., Wai, S. N., . . . Johannessen, M. (2019). Comparative exoproteome profiling of an invasive and a commensal Staphylococcus haemolyticus isolate. Journal of Proteomics, 197, 106-114
Open this publication in new window or tab >>Comparative exoproteome profiling of an invasive and a commensal Staphylococcus haemolyticus isolate
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2019 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 197, p. 106-114Article in journal (Refereed) Published
Abstract [en]

Staphylococcus haemolyticus is a skin commensal emerging as an opportunistic pathogen. Nosocomial isolates of S. haemolyticus are the most antibiotic resistant members of the coagulase negative staphylococci (CoNS), but information about other S. haemolyticus virulence factors is scarce. Bacterial membrane vesicles (MVs) are one mediator of virulence by enabling secretion and long distance delivery of bacterial effector molecules while protecting the cargo from proteolytic degradation from the environment. We wanted to determine if the MV protein cargo of S. haemolyticus is strain specific and enriched in certain MV associated proteins compared to the totalsecretome.

The present study shows that both clinical and commensal S. haemolyticus isolates produce membrane vesicles. The MV cargo of both strains was enriched in proteins involved in adhesion and acquisition of iron. The MV cargo of the clinical strain was further enriched in antimicrobial resistance proteins.

Data are available via ProteomeXchange with identifier PXD010389.

Biological significance: Clinical isolates of Staphylococcus haemolyticus are usually multidrug resistant, their main virulence factor is formation of biofilms, both factors leading to infections that are difficult to treat. We show that both clinical and commensal S. haemolyticusisolates produce membrane vesicles. Identification of staphylococcal membrane vesicles can potentially be used in novel approaches to combat staphylococcal infections, such as development of vaccines.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Staphylococcus haemolyticus, Opportunistic pathogen, Membrane, Vesicle cargo, Total secretome, Virulence factors
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-158067 (URN)10.1016/j.jprot.2018.11.013 (DOI)000462108200011 ()30472255 (PubMedID)
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved
Cavanagh, J. P., Askarian, F., Pain, M., Bruun, J.-A., Urbarova, I., Wai, S. N., . . . Johannessen, M. (2019). Proteome profiling of secreted and membrane vesicle associated proteins of an invasive and a commensal Staphylococcus haemolyticus isolate. Data in Brief, 22, 914-919
Open this publication in new window or tab >>Proteome profiling of secreted and membrane vesicle associated proteins of an invasive and a commensal Staphylococcus haemolyticus isolate
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2019 (English)In: Data in Brief, E-ISSN 2352-3409, Vol. 22, p. 914-919Article in journal (Refereed) Published
Abstract [en]

Bacterial membrane vesicles (MVs) mediate bacterial virulence by enabling secretion and long distance delivery of bacterial effector molecules. Staphylococcus haemolyticus has now been demonstrated to produce membrane vesicles (MVs). The protein content of S. haemolyticus MVs was identified by Mass spectrometry and compared to proteins identified in the total secretome. This information is presented in this data article. Further background and interpretation of the data can be found in the article: Comparative exoproteome profiling of an invasive and a commensal S. haemolyticus isolate (Cavanagh et al., in press). Data are available via Proteome Xchange with identifier PXD010389.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-162514 (URN)10.1016/j.dib.2018.11.147 (DOI)000458114600124 ()30766906 (PubMedID)
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved
Lindholm, M., Aung, K. M., Wai, S. N. & Oscarsson, J. (2019). Role of OmpA1 and OmpA2 in Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus serum resistance. Journal of Oral Microbiology, 11(1), Article ID 1536192.
Open this publication in new window or tab >>Role of OmpA1 and OmpA2 in Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus serum resistance
2019 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 11, no 1, article id 1536192Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus belong to the HACEK group of fastidious Gram-negative organisms, a recognized cause of infective endocarditis. A. actinomycetemcomitans is also implicated in aggressive forms of periodontitis. We demonstrated that A. aphrophilus strains, as A. actinomycetemcomitans are ubiquitously serum resistant. Both species encode two Outer membrane protein A paralogues, here denoted OmpA1 and OmpA2. As their respective pangenomes contain several OmpA1 and OmpA2 alleles, they represent potential genotypic markers. A naturally competent strain of A. actinomycetemcomitans and A. aphrophilus, respectively were used to elucidate if OmpA1 and OmpA2 contribute to serum resistance. Whereas OmpA1 was critical for survival of A. actinomycetemcomitans D7SS in 50% normal human serum (NHS), serum resistant ompA1 mutants were fortuitously obtained, expressing enhanced levels of OmpA2. Similarly, OmpA1 rather than OmpA2 was a major contributor to serum resistance of A. aphrophilus HK83. Far-Western blot revealed that OmpA1AA, OmpA2AA, and OmpA1AP can bind to C4-binding protein, an inhibitor of classical and mannose-binding lectin (MBL) complement activation. Indeed, ompA1 mutants were susceptible to these pathways, but also to alternative complement activation. This may at least partly reflect a compromised outer membrane integrity but is also consistent with alternative mechanisms involved in OmpA-mediated serum resistance.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, serum resistance, outer membrane protein A
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-153103 (URN)10.1080/20002297.2018.1536192 (DOI)000448422100001 ()2-s2.0-85055581204 (Scopus ID)
Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2018-11-07Bibliographically approved
Larsson, P., Khaja, A. S., Semenas, J., Wang, T., Sarwar, M., Dizeyi, N., . . . Persson, J. L. (2019). The functional interlink between AR and MMP9/VEGF signaling axis is mediated through PIP5K1 alpha/pAKT in prostate cancer. International Journal of Cancer
Open this publication in new window or tab >>The functional interlink between AR and MMP9/VEGF signaling axis is mediated through PIP5K1 alpha/pAKT in prostate cancer
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed) Epub ahead of print
Abstract [en]

Currently, no effective targeted therapeutics exists for treatment of metastatic prostate cancer (PCa). Given that matrix metalloproteinases 9 (MMP9) and its associated vascular endothelial growth factor (VEGF) are critical for tumor vascularization and invasion under castration-resistant condition, it is therefore of great importance to define the functional association and interplay between androgen receptor (AR) and MMP9 and their associated key survival and invasion pathways in PCa cells. Here, we found that there was a significant correlation between MMP9 and AR protein expression in primary and metastatic PCa tissues, and a trend that high level of MMP9 expression was associated with poor prognosis. We demonstrated that constitutive activation of AR increased expression of MMP9 and VEGF/VEGF receptors. We further showed that AR exerts its effect on MMP9/VEGF signaling axis through PIP5K1 alpha/AKT. We showed that MMP9 physically interacted with PIP5K1 alpha via formation of protein-protein complexes. Furthermore, elevated expression of MMP9 enhanced ability of AR to activate its target gene cyclin A1. The elevated sequential activation of AR/PIP5K1 alpha/AKT/MMP9/VEGF signaling axis contributed to increased invasiveness and growth of metastatic tumors. Conversely, treatment with PIP5K1 alpha inhibitor significantly suppressed invasiveness of PCa cells expressing constitutively activated AR, this was coincident with its inhibitory effect of this inhibitor on AR/MMP9/VEGF pathways. Our results suggest that AR and MMP9-associated network proteins may be effectively targeted by blocking PIP5K1 alpha/AKT pathways using PIP5K1 alpha inhibitor in metastatic PCa.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
matrix metalloproteinases 9, AKT, androgen receptor, metastatic prostate cancer, targeted therapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-162846 (URN)10.1002/ijc.32607 (DOI)000481247000001 ()31381135 (PubMedID)
Available from: 2019-09-11 Created: 2019-09-11 Last updated: 2019-09-11
Bitar, A., Aung, K. M., Wai, S. N. & Hammarström, M.-L. (2019). Vibrio cholerae derived outer membrane vesicles modulate the inflammatory response of human intestinal epithelial cells by inducing microRNA-146a. Scientific Reports, 9, Article ID 7212.
Open this publication in new window or tab >>Vibrio cholerae derived outer membrane vesicles modulate the inflammatory response of human intestinal epithelial cells by inducing microRNA-146a
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7212Article in journal (Refereed) Published
Abstract [en]

The small intestinal epithelium of Vibrio cholerae infected patients expresses the immunomodulatory microRNAs miR-146a and miR-155 at acute stage of disease. V. cholerae release outer membrane vesicles (OMVs) that serve as vehicles for translocation of virulence factors including V. cholerae cytolysin (VCC). The aim was to investigate whether OMVs, with and/or without VCC-cargo could be responsible for induction of microRNAs in intestinal epithelial cells and thereby contribute to immunomodulation. Polarized tight monolayers of T84 cells were challenged with OMVs of wildtype and a VCC deletion mutant of the non-O1/non-O139 (NOVC) V. cholerae strain V:5/04 and with soluble VCC. OMVs, with and without VCC-cargo, caused significantly increased levels of miR-146a. Increase was seen already after 2 hours challenge with OMVs and persisted after 12 hours. Challenge with soluble VCC caused significant increases in interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), CCL20, IL-1β, and IRAK2 mRNA levels while challenge with OMVs did not cause increases in expression levels of any of these mRNAs. These results suggest that V. cholerae bacteria release OMVs that induce miR-146a in order to pave the way for colonization by reducing the strength of an epithelial innate immune defence reaction and also preventing inflammation in the mucosa that factors like VCC can evoke.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-159266 (URN)10.1038/s41598-019-43691-9 (DOI)000467543700027 ()31076615 (PubMedID)2-s2.0-85065655754 (Scopus ID)
Available from: 2019-05-23 Created: 2019-05-23 Last updated: 2019-06-19Bibliographically approved
Taheri, N., Mahmud, A. K., Sandblad, L., Fällman, M., Wai, S. N. & Fahlgren, A. (2018). Campylobacter jejuni bile exposure influences outer membrane vesicles protein content and bacterial interaction with epithelial cells. Scientific Reports, 8, Article ID 16996.
Open this publication in new window or tab >>Campylobacter jejuni bile exposure influences outer membrane vesicles protein content and bacterial interaction with epithelial cells
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16996Article in journal (Refereed) Published
Abstract [en]

Campylobacter jejuni is a prevalent human pathogen and a major cause of bacterial gastroenteritis in the world. In humans, C. jejuni colonizes the intestinal tract and its tolerance to bile is crucial for bacteria to survive and establish infection. C. jejuni produces outer membrane vesicles (OMVs) which have been suggested to be involved in virulence. In this study, the proteome composition of C. jejuni OMVs in response to low concentration of bile was investigated. We showed that exposure of C. jejuni to low concentrations of bile, similar to the concentration in cecum, induced significant changes in the protein profile of OMVs released during growth without affecting the protein profile of the bacteria. This suggests that bile influences a selective packing of the OMVs after bacterial exposure to low bile. A low concentration of bile was found to increase bacterial adhesion to intestinal epithelial cells, likely by an enhanced hydrophobicity of the cell membrane following exposure to bile. The increased bacterial adhesiveness was not associated with increased invasion, instead bile exposure decreased C. jejuni invasion. OMVs released from bacteria upon exposure to low bile showed to increase both adhesion and invasion of non-bile-exposed bacteria into intestinal epithelial cells. These findings suggest that C. jejuni in environments with low concentrations of bile produce OMVs that facilitates colonization of the bacteria, and this could potentially contribute to virulence of C. jejuni in the gut.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Microbiology Cell Biology
Identifiers
urn:nbn:se:umu:diva-153787 (URN)10.1038/s41598-018-35409-0 (DOI)000450411700027 ()
Funder
Carl Tryggers foundation
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2019-01-18Bibliographically approved
Nakao, R., Myint, S. L., Wai, S. N. & Uhlin, B. E. (2018). Enhanced Biofilm Formation and Membrane Vesicle Release by Escherichia coli Expressing a Commonly Occurring Plasmid Gene, kil. Frontiers in Microbiology, 9, Article ID 2605.
Open this publication in new window or tab >>Enhanced Biofilm Formation and Membrane Vesicle Release by Escherichia coli Expressing a Commonly Occurring Plasmid Gene, kil
2018 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 2605Article in journal (Refereed) Published
Abstract [en]

Escherichia coli is one of the most prevalent microorganisms forming biofilms on indwelling medical devices, as well as a representative model to study the biology and ecology of biofilms. Here, we report that a small plasmid gene, kil, enhances biofilm formation of E coli. The kil gene is widely conserved among naturally occurring colicinogenic plasmids such as ColE1 plasmid, and is also present in some plasmid derivatives used as cloning vectors. First, we found that overexpression of the kil gene product dramatically increased biofilm mass enriched with extracellular DNA in the outer membrane-compromised strain RN102, a deep rough LPS mutant E. coli K-12 derivative. We also found that the kil-enhanced biofilm formation was further promoted by addition of physiologically relevant concentrations of Mg2+, not only in the case of RN102, but also with the parental strain BW25113, which retains intact core-oligosaccharide LPS. Biofilm formation by kil-expressing BW25113 strain (BW25113 kil+) was significantly inhibited by protease but not DNase I. In addition, a large amount of proteinous materials were released from the BW25113 kil+ cells. These materials contained soluble cytoplasmic and periplasmic proteins, and insoluble membrane vesicles (MVs). The kil-induced MVs were composed of not only outer membrane/periplasmic proteins, but also inner membrane/cytoplasmic proteins, indicating that MVs from both of the outer and inner membranes could be released into the extracellular milieu. Subcellular fractionation analysis revealed that the Kil proteins translocated to both the outer and inner membranes in whole cells of BW25113 kil+. Furthermore, the BW25113 kil+ showed not only reduced viability in the stationary growth phase, but also increased susceptibility to killing by predator bacteria, Vibrio cholerae expressing the type VI secretion system, despite no obvious change in morphology and physiology of the bacterial membrane under regular culture conditions. Taken together, our findings suggest that there is risk of increasing biofilm formation and spreading of numerous MVs releasing various cellular components due to kil gene expression. From another point of view, our findings could also offer efficient MV production strategies using a conditional kil vector in biotechnological applications.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
Escherichia coli, bacterial biofilms, membrane vesicles, kil, ColE1 plasmids
National Category
Microbiology Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-153543 (URN)10.3389/fmicb.2018.02605 (DOI)000449415700001 ()
Funder
Swedish Research Council, 2015-03007Swedish Research Council, 2015-06824Swedish Research Council, 2014-4401Swedish Research Council, 2016-06598Swedish Research Council, 349-2007-8673Swedish Research CouncilThe Kempe Foundations
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Dongre, M., Singh, B., Aung, K. M., Larsson, P., Miftakhova, R. R., Persson, K., . . . Wai, S. N. (2018). Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts. Communications Biology, 1, Article ID 59.
Open this publication in new window or tab >>Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts
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2018 (English)In: Communications Biology, ISSN 2399-3642, Vol. 1, article id 59Article in journal (Refereed) Published
Abstract [en]

Using Caenorhabditis elegans as an infection host model for Vibrio cholerae predator interactions, we discovered a bacterial cytotoxin, MakA, whose function as a virulence factor relies on secretion via the flagellum channel in a proton motive force-dependent manner. The MakA protein is expressed from the polycistronic makDCBA (motility-associated killing factor) operon. Bacteria expressing makDCBA induced dramatic changes in intestinal morphology leading to a defecation defect, starvation and death in C. elegans. The Mak proteins also promoted V. cholerae colonization of the zebrafish gut causing lethal infection. A structural model of purified MakA at 1.9 Å resolution indicated similarities to members of a superfamily of bacterial toxins with unknown biological roles. Our findings reveal an unrecognized role for V. cholerae flagella in cytotoxin export that may contribute both to environmental spread of the bacteria by promoting survival and proliferation in encounters with predators, and to pathophysiological effects during infections.

Place, publisher, year, edition, pages
Springer Nature Publishing AG, 2018
National Category
Microbiology in the medical area
Research subject
Infectious Diseases; Molecular Biology
Identifiers
urn:nbn:se:umu:diva-155563 (URN)10.1038/s42003-018-0065-z (DOI)000461126500059 ()30271941 (PubMedID)
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-04-04Bibliographically approved
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