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The Pseudomonas aeruginosa T6SS delivers a periplasmic toxin that disrupts bacterial cell morphology

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Title: The Pseudomonas aeruginosa T6SS delivers a periplasmic toxin that disrupts bacterial cell morphology
Authors: Wood, TE
Howard, SA
Forster, A
Nolan, LM
Manoli, E
Bullen, NP
Yau, HCL
Hachani, A
Hayward, RD
Whitney, JC
Vollmer, W
Freemont, PS
Filloux, A
Item Type: Journal Article
Abstract: The type VI secretion system (T6SS) is crucialin interbacterial competition and is avirulence determinant ofmany Gram-negative bacteria. Several T6SS effectorsarecovalently fused to secreted T6SS structural components such asthe VgrG spike for delivery into target cells.In Pseudomonas aeruginosa, theVgrG2b effector waspreviously proposedto mediatebacterial internalisation into eukaryotic cells. In this work, wefind that the VgrG2b C-terminal domain(VgrG2bC-ter) elicits toxicity in the bacterial periplasm, counteracted by a cognate immunity protein.We resolve thestructure of VgrG2bC-ter and confirm it is a member ofthezinc-metallopeptidasefamily of enzymes. We show that this effector causesmembrane blebbing atmidcell, whichsuggests a distincttype of T6SS-mediated growthinhibition through interference with cell division, mimicking the impact of β-lactam antibiotics. Ourstudyintroduces a further effector family to the T6SS arsenaland demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells.
Issue Date: 1-Oct-2019
Date of Acceptance: 27-Aug-2019
URI: http://hdl.handle.net/10044/1/73329
DOI: 10.1016/j.celrep.2019.08.094
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 187
End Page: 201.e7
Journal / Book Title: Cell Reports
Volume: 29
Issue: 1
Copyright Statement: © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Medical Research Council (MRC)
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/K001930/1
625318
MR/N023250/1
MR/P028225/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
VI-SECRETION-SYSTEM
ESCHERICHIA-COLI
MUTANTS LACKING
SUICIDE VECTOR
INDUCED LYSIS
PROTEIN
EFFECTOR
GENE
TARGET
SEPARATION
Pseudomonas aeruginosa
VgrG
effector
metallopeptidase
type VI secretion system
Anti-Bacterial Agents
Bacterial Proteins
Bacterial Secretion Systems
Periplasm
Pseudomonas aeruginosa
Type VI Secretion Systems
Virulence Factors
beta-Lactams
Periplasm
Pseudomonas aeruginosa
beta-Lactams
Bacterial Proteins
Virulence Factors
Anti-Bacterial Agents
Bacterial Secretion Systems
Type VI Secretion Systems
0601 Biochemistry and Cell Biology
1116 Medical Physiology
Publication Status: Published
Online Publication Date: 2019-10-01
Appears in Collections:Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences