title: Centrality in the host-pathogen interactome is associated with pathogen fitness during infection.
abstract: 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.
authors.affiliation: Systems Biology of Infection Lab, Department of Microbiology, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Crua Asensio
authors.affiliation: Systems Biology of Infection Lab, Department of Microbiology, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Muñoz Giner
authors.affiliation: Gene Function and Evolution Lab, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Natalia Sánchez
authors.initials: NS
authors.lastname: de Groot
authors.affiliation: Systems Biology of Infection Lab, Department of Microbiology, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, Department of Biochemistry and Molecular Biology, Biosciences Faculty, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Torrent Burgas
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D010930:Plague / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015010:Yersinia pestis / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins