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


METHODS
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.


CONCLUSIONS
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.
Dyer
Matthew D
MD
Virginia Bioinformatics Institute, Blacksburg, Virginia, United States of America.
Neff
Chris
C
Dufford
Max
M
Rivera
Corban G
CG
Shattuck
Donna
D
Bassaganya-Riera
Josep
J
Murali
T M
TM
Sobral
Bruno W
BW
D001408:Bacillus anthracis / Q000378:metabolism* / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D019295:Computational Biology; D005604:Francisella tularensis / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D015010:Yersinia pestis / Q000378:metabolism* / Q000502:physiology
D001426:Bacterial Proteins