title: Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.
abstract: A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.
authors.affiliation: Laboratory of Analytical Microbiology, State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Ke
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tan
authors.forename: Sebenzile K
authors.initials: SK
authors.lastname: Myeni
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Shi
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Zhaobiao
authors.initials: Z
authors.lastname: Guo
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
authors.forename: Zongmin
authors.initials: Z
authors.lastname: Du
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D019295:Computational Biology; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D010930:Plague / Q000276:immunology* / Q000382:microbiology*; D011485:Protein Binding; D014774:Virulence; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins