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

DOI: 10.1016/j.celrep.2019.08.094

Authors: Thomas E. Wood (Imperial College London) , Sophie A. Howard (Imperial College London) , Andreas Forster (Imperial College London) , Laura M. Nolan (Imperial College London) , Eleni Manoli (Imperial College London) , Nathan P. Bullen (McMaster University) , Hamish C. L. Yau (Newcastle University) , Abderrahman Hachani (Imperial College London) , Richard D. Hayward (University of Cambridge) , John C. Whitney (McMaster University) , Waldemar Vollmer (Newcastle University) , Paul S. Freemont (Imperial College London) , Alain Filloux (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports , VOL 29 , PAGES 187 - 201.e7

State: Published (Approved)
Published: October 2019

Abstract: The type VI secretion system (T6SS) is crucial in interbacterial competition and is a virulence determinant of many Gram-negative bacteria. Several T6SS effectors are covalently fused to secreted T6SS structural components such as the VgrG spike for delivery into target cells. In Pseudomonas aeruginosa, the VgrG2b effector was previously proposed to mediate bacterial internalization into eukaryotic cells. In this work, we find that the VgrG2b C-terminal domain (VgrG2bC-ter) elicits toxicity in the bacterial periplasm, counteracted by a cognate immunity protein. We resolve the structure of VgrG2bC-ter and confirm it is a member of the zinc-metallopeptidase family of enzymes. We show that this effector causes membrane blebbing at midcell, which suggests a distinct type of T6SS-mediated growth inhibition through interference with cell division, mimicking the impact of β-lactam antibiotics. Our study introduces a further effector family to the T6SS arsenal and demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells.

Journal Keywords: type VI secretion system; VgrG; effector; metallopeptidase; Pseudomonas aeruginosa

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 24/10/2019 15:23

Documents:
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Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags: