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Updated: Mar 8, 2026
A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Centrality in the host-pathogen interactome is associated with pathogen fitness during infection
Núria Crua Asensio1, Elisabet Muñoz Giner1, Natalia Sánchez de Groot2,3
1Systems Biology of Infection Lab, Department of Microbiology, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
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.
Insights
Protein interactions within the host-pathogen interactome are crucial for bacterial infection. High connectivity, or
Area of Science:
- Microbiology
- Systems Biology
- Infectious Diseases
Background:
- Protein interactions are essential for cellular functions.
- The role of host-pathogen protein interactions in bacterial infection dynamics is not fully understood.
- Understanding these interactions can reveal pathogen vulnerabilities.
Purpose of the Study:
- To investigate the relationship between protein interaction network connectivity and pathogen fitness during infection.
- To determine if the centrality-lethality rule applies to pathogen proteins within the context of the host-pathogen interactome.
- To identify potential antimicrobial drug targets based on protein interaction network properties.
Main Methods:
- Utilized Yersinia pestis as a model organism for bacterial infection studies.
- Analyzed the host-pathogen interactome to map protein-protein interactions.
- Applied network analysis metrics, including centrality, to evaluate protein importance.
- Correlated protein connectivity with pathogen fitness during infection.
Main Results:
- Pathogen protein connectivity within the host-pathogen interactome directly correlates with pathogen fitness.
- The centrality-lethality rule is applicable to pathogen fitness when considering host-pathogen interactions.
- Pathogen proteins with a higher number of host interactions are more critical for infection.
- Proteins that extensively rewire the host interactome have a significant impact on pathogen fitness.
Conclusions:
- Protein interaction network topology is a key determinant of pathogen success during infection.
- Hub proteins in the host-pathogen interactome represent promising targets for novel antimicrobial therapies.
- Targeting highly connected pathogen proteins could disrupt infection mechanisms and reduce virulence.
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