Centrality in the host-pathogen interactome is associated with pathogen fitness during infection

To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.M.T.B. would like to acknowledge support from the Programa Ramón y Cajal (RYC-2012-09999). This study has been funded by the Ministerio de Economía y Competitividad (SAF2014-56568-R) and a Research Grant 2016 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) both to M.T.B. N.S.d.G acknowledges support of the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017' and CERCA Programme from the Generalitat de Catalunya