A family of Type VI secretion system effector proteins that form ion-selective pores

Giuseppina Mariano; Katharina Trunk; David J. Williams; Laura Monlezun; Henrik Strahl; Samantha J.  Pitt; Sarah Coulthurst

doi:10.1038/s41467-019-13439-0

A family of Type VI secretion system effector proteins that form ion-selective pores

Giuseppina Mariano, Katharina Trunk, David J. Williams, Laura Monlezun, Henrik Strahl, Samantha J. Pitt, Sarah Coulthurst (Lead / Corresponding author)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

171 Downloads (Pure)

Abstract

Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.

Original language	English
Article number	5484
Pages (from-to)	1-15
Number of pages	15
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13439-0
Publication status	Published - 2 Dec 2019

Keywords

Bacterial secretion
Bacterial toxins
Bacteriology
Ion channels

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-019-13439-0Licence: CC BY

Final Published VersionFinal published version, 1.97 MBLicence: CC BY

Cite this

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title = "A family of Type VI secretion system effector proteins that form ion-selective pores",

abstract = "Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.",

keywords = "Bacterial secretion, Bacterial toxins, Bacteriology, Ion channels",

author = "Giuseppina Mariano and Katharina Trunk and Williams, {David J.} and Laura Monlezun and Henrik Strahl and Pitt, {Samantha J.} and Sarah Coulthurst",

note = "This work was supported by the Wellcome Trust (104556/Z/14/Z, Senior Fellowship in Basic Biomedical Science to S.J.C.; 097818/Z/11/B and 109118/Z/15/Z, PhD studentships to University of Dundee), the MRC (MR/K000111X/1, New Investigator Research Grant to S.J.C.) and the Royal Society of Edinburgh (Biomedical Personal Research Fellowship to S.J.P.). We thank Roland Freudl for the gift of anti-OmpA antibody; Adam Ostrowski for construction of strains AO07 and AO08; Gal Horesh, Amy Dorward and Gavin Robertson for expert assistance; the Flow Cytometry and Cell Sorting Facility at the University of Dundee; and the Dundee Imaging Facility (supported by Wellcome Trust [097945/B/11/Z] and MRC [MR/K015869/1]) awards).",

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AU - Mariano, Giuseppina

AU - Trunk, Katharina

AU - Williams, David J.

AU - Monlezun, Laura

AU - Strahl, Henrik

AU - Pitt, Samantha J.

AU - Coulthurst, Sarah

N1 - This work was supported by the Wellcome Trust (104556/Z/14/Z, Senior Fellowship in Basic Biomedical Science to S.J.C.; 097818/Z/11/B and 109118/Z/15/Z, PhD studentships to University of Dundee), the MRC (MR/K000111X/1, New Investigator Research Grant to S.J.C.) and the Royal Society of Edinburgh (Biomedical Personal Research Fellowship to S.J.P.). We thank Roland Freudl for the gift of anti-OmpA antibody; Adam Ostrowski for construction of strains AO07 and AO08; Gal Horesh, Amy Dorward and Gavin Robertson for expert assistance; the Flow Cytometry and Cell Sorting Facility at the University of Dundee; and the Dundee Imaging Facility (supported by Wellcome Trust [097945/B/11/Z] and MRC [MR/K015869/1]) awards).

PY - 2019/12/2

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N2 - Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.

AB - Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.

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A family of Type VI secretion system effector proteins that form ion-selective pores

Abstract

Keywords

ASJC Scopus subject areas

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Wellcome Trust PhD Studentship

Deployment Consequences and Utility of Bacterial Effectors (Senior Research Fellowship)

Stabilising G-Protein Coupled Receptors in Solution With Cholesterol-Based Detergents for Drug Discovery Purposes

Coulthurst, Sarah

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A family of Type VI secretion system effector proteins that form ion-selective pores

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Wellcome Trust PhD Studentship

Deployment Consequences and Utility of Bacterial Effectors (Senior Research Fellowship)

Stabilising G-Protein Coupled Receptors in Solution With Cholesterol-Based Detergents for Drug Discovery Purposes

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Coulthurst, Sarah

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