Type III secretion system effectors form robust and flexible intracellular virulence networks
File(s)
Accepted version
Supporting information
Author(s)
Ruano-Gallego, David
Sanchez-Garrido, Julia
Kozik, Zuzanna
Nunez-Berrueco, Elena
Cepeda-Molero, Massiel
Type
Journal Article
Abstract
Infections with many Gram-negative pathogens, including Escherichia coli, Salmonella, Shigella, and Yersinia, rely on type III secretion system (T3SS) effectors. We hypothesized that while hijacking processes within mammalian cells, the effectors operate as a robust network that can tolerate substantial contractions. This was tested in vivo using the mouse pathogen Citrobacter rodentium (encoding 31 effectors). Sequential gene deletions showed that effector essentiality for infection was context dependent and that the network could tolerate 60% contraction while maintaining pathogenicity. Despite inducing very different colonic cytokine profiles (e.g., interleukin-22, interleukin-17, interferon-γ, or granulocyte-macrophage colony-stimulating factor), different networks induced protective immunity. Using data from >100 distinct mutant combinations, we built and trained a machine learning model able to predict colonization outcomes, which were confirmed experimentally. Furthermore, reproducing the human-restricted enteropathogenic E. coli effector repertoire in C. rodentium was not sufficient for efficient colonization, which implicates effector networks in host adaptation. These results unveil the extreme robustness of both T3SS effector networks and host responses.
Date Issued
2021-03-12
Date Acceptance
2021-03-01
Citation
Science, 2021, 371 (6534), pp.1-21
ISSN
0036-8075
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Start Page
1
End Page
21
Journal / Book Title
Science
Volume
371
Issue
6534
Copyright Statement
© 2021 The Author(s)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000630096400024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Publication Status
Published
Date Publish Online
2021-03-12