Envelope stress responses defend against type six secretion system attacks independently of immunity proteins

The arms race among microorganisms is a key driver in the evolution of not only the weapons but also defence mechanisms. Many Gram-negative bacteria use the type six secretion system (T6SS) to deliver toxic effectors directly into neighbouring cells. Defence against effectors requires cognate immuni...

Full description

Saved in:
Bibliographic Details
Published inNature microbiology Vol. 5; no. 5; pp. 706 - 714
Main Authors Hersch, Steven J., Watanabe, Nobuhiko, Stietz, Maria Silvina, Manera, Kevin, Kamal, Fatima, Burkinshaw, Brianne, Lam, Linh, Pun, Alexander, Li, Meixin, Savchenko, Alexei, Dong, Tao G.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.05.2020
Nature Publishing Group
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:The arms race among microorganisms is a key driver in the evolution of not only the weapons but also defence mechanisms. Many Gram-negative bacteria use the type six secretion system (T6SS) to deliver toxic effectors directly into neighbouring cells. Defence against effectors requires cognate immunity proteins. However, here we show immunity-independent protection mediated by envelope stress responses in Escherichia coli and Vibrio cholerae against a V. cholerae T6SS effector, TseH. We demonstrate that TseH is a PAAR-dependent species-specific effector highly potent against Aeromonas species but not against its V. cholerae immunity mutant or E. coli . A structural analysis reveals TseH is probably a NlpC/P60-family cysteine endopeptidase. We determine that two envelope stress-response pathways, Rcs and BaeSR, protect E. coli from TseH toxicity by mechanisms including capsule synthesis. The two-component system WigKR (VxrAB) is critical for protecting V. cholerae from its own T6SS despite expressing immunity genes. WigR also regulates T6SS expression, suggesting a dual role in attack and defence. This deepens our understanding of how bacteria survive T6SS attacks and suggests that defence against the T6SS represents a major selective pressure driving the evolution of species-specific effectors and protective mechanisms mediated by envelope stress responses and capsule synthesis. Defence against type six secretion system (T6SS) effectors is thought to be mostly mediated by dedicated immunity proteins that antagonize specific effector proteins. Here, two envelope stress-response pathways, Rcs and BaeSR, are shown to regulate protection against the T6SS effector TseH by modulating the integrity of the bacterial envelope in a manner independent of immunity proteins.
Bibliography:S.J.H. designed, performed and analysed most of the biological experiments and prepared the manuscript and figures. N.W. and A.S. performed and analysed the crystallography. M.S.S. performed the microscopy. K.M. performed and analysed the RT-qPCR. F.K. performed the permeability analysis, helped construct plasmids and identified reduced toxicity TseH mutants. B.B. performed and analyzed the pull-down assays. L.L. analysed genome sequencing data. A.P. and M.L. helped construct strains and plasmids. N.W., A.S. and T.G.D. contributed to manuscript revision. T.G.D. conceived the project and supervised the study.
Author contributions
ISSN:2058-5276
2058-5276
DOI:10.1038/s41564-020-0672-6