The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pesti

dc.contributor.authorDye, Matthew D.en
dc.contributor.authorNeff, Chrisen
dc.contributor.authorDufford, Maxen
dc.contributor.authorRivera, Corban G.en
dc.contributor.authorShattuck, Donnaen
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.authorMurali, T. M.en
dc.contributor.authorSobral, Brunoen
dc.date.accessed2014-05-01en
dc.date.accessioned2014-06-17T20:12:05Zen
dc.date.available2014-06-17T20:12:05Zen
dc.date.issued2010-08-09en
dc.description.abstractBackground: Bacillus anthracis, Francisella tularensis, and Yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as NIAID Category A priority pathogens for possible use as biological weapons. However, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion. Methodology: In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions between human proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, we identified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactions including interactions involving 304 B. anthracis, 52 F. tularensis, and 330 Y. pestis proteins that are uncharacterized. Computational analysis revealed that pathogen proteins preferentially interact with human proteins that are hubs and bottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conserved amongst the three networks. Functionally, such conserved modules reveal commonalities between how the different pathogens interact with crucial host pathways involved in inflammation and immunity. Significance: These data constitute the first extensive protein interaction networks constructed for bacterial pathogens and their human hosts. This study provides novel insights into host-pathogen interactions.en
dc.description.sponsorshiphis project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200900040C to Bruno Sobral and contract DHHSN266200400057C to Myriad. Facilities and equipment for doing the experiments was provided by Myriad, INC. Time for CN, MD, and DS was partially funded by Myriad, INC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationDyer MD, Neff C, Dufford M, Rivera CG, Shattuck D, et al. (2010) The Human-Bacterial Pathogen Protein Interaction Networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis. PLoS ONE 5(8): e12089. doi:10.1371/journal.pone.0012089en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0012089en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/10919/48979en
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012089en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBacterial pathologyen
dc.subjectCentralityen
dc.subjectFrancisella tularensisen
dc.subjectHost-pathogen interactionsen
dc.subjectImmune response|Protein interaction networksen
dc.subjectProtein interactionsen
dc.subjectYersinia pestisen
dc.titleThe human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestien
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden

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