Type III secretion system effectors form robust and flexible intracellular virulence networks.

Autor: Ruano-Gallego D; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Sanchez-Garrido J; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Kozik Z; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, UK., Núñez-Berrueco E; Laboratorio de Inteligencia Artificial, Departamento de Inteligencia Artificial, Universidad Politécnica de Madrid, Campus de Montegancedo, Boadilla del Monte, Madrid, Spain., Cepeda-Molero M; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Mullineaux-Sanders C; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Naemi Baghshomali Y; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Slater SL; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Wagner N; The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Glegola-Madejska I; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK., Roumeliotis TI; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, UK., Pupko T; The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Fernández LÁ; Centro Nacional de Biotecnología (CNB-CSIC), Department of Microbial Biotechnology, Madrid, Spain., Rodríguez-Patón A; Laboratorio de Inteligencia Artificial, Departamento de Inteligencia Artificial, Universidad Politécnica de Madrid, Campus de Montegancedo, Boadilla del Monte, Madrid, Spain., Choudhary JS; Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, UK. g.frankel@imperial.ac.uk jyoti.choudhary@icr.ac.uk., Frankel G; Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College, London, UK. g.frankel@imperial.ac.uk jyoti.choudhary@icr.ac.uk.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Mar 12; Vol. 371 (6534).
DOI: 10.1126/science.abc9531
Abstrakt: 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.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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