The Human-Bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis

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Abstract

Background: 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 forpossible use as biological weapons. However, the interactions between human proteins and proteins in these bacteriaremain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immuneevasion.Methodology: In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions betweenhuman proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, weidentified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactionsincluding 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 andbottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conservedamongst the three networks. Functionally, such conserved modules reveal commonalities between how the differentpathogens interact with crucial host pathways involved in inflammation and immunity.Significance: These data constitute the first extensive protein interaction networks constructed for bacterial pathogens andtheir human hosts. This study provides novel insights into host-pathogen interactions. © 2010 Dyer et al.

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Dyer, M. D., Nef, C., Dufford, M., Rivera, C. G., Shattuck, D., Bassaganya-Riera, J., … Sobral, B. W. (2010). The Human-Bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis. PLoS ONE, 5(8). https://doi.org/10.1371/journal.pone.0012089

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