@article{Ruano-Gallego:2021:10.1126/science.abc9531,
author = {Ruano-Gallego, D and Sanchez-Garrido, J and Kozik, Z and Nunez-Berrueco, E and Cepeda-Molero, M and Mullineaux-Sanders, C and Naemi-Baghshomali, Clark J and Slater, SL and Wagner, N and Glegola-Madejska, I and Roumeliotis, T and Pupko, T and Angel, Fernandez L and Rodriguez-Paton, A and Choudhary, JS and Frankel, G},
doi = {10.1126/science.abc9531},
journal = {Science},
pages = {1--21},
title = {Type III secretion system effectors form robust and flexible intracellular virulence networks},
url = {http://dx.doi.org/10.1126/science.abc9531},
volume = {371},
year = {2021}
}

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TY  - JOUR
AB  - 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.
AU  - Ruano-Gallego,D
AU  - Sanchez-Garrido,J
AU  - Kozik,Z
AU  - Nunez-Berrueco,E
AU  - Cepeda-Molero,M
AU  - Mullineaux-Sanders,C
AU  - Naemi-Baghshomali,Clark J
AU  - Slater,SL
AU  - Wagner,N
AU  - Glegola-Madejska,I
AU  - Roumeliotis,T
AU  - Pupko,T
AU  - Angel,Fernandez L
AU  - Rodriguez-Paton,A
AU  - Choudhary,JS
AU  - Frankel,G
DO  - 10.1126/science.abc9531
EP  - 21
PY  - 2021///
SN  - 0036-8075
SP  - 1
TI  - Type III secretion system effectors form robust and flexible intracellular virulence networks
T2  - Science
UR  - http://dx.doi.org/10.1126/science.abc9531
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000630096400024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.science.org/doi/10.1126/science.abc9531
UR  - http://hdl.handle.net/10044/1/94617
VL  - 371
ER  - 

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