Journal article

The Pseudomonas aeruginosa T6SS Delivers a Periplasmic Toxin that Disrupts Bacterial Cell Morphology

Thomas E Wood, Sophie A Howard, Andreas Forster, Laura M Nolan, Eleni Manoli, Nathan P Bullen, Hamish CL Yau, Abderrahman Hachani, Richard D Hayward, John C Whitney, Waldemar Vollmer, Paul S Freemont, Alain Filloux

CELL REPORTS | CELL PRESS | Published : 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..

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University of Melbourne Researchers

Grants

Awarded by MRC


Awarded by Marie Curie Fellowship


Awarded by Wellcome Trust


Awarded by H2020-MSCA-Global Fellowship


Awarded by Canadian Institutes of Health Research (CIHR)


Funding Acknowledgements

The authors are grateful to Luke P. Allsopp, Sarah Wettstadt, and Silvia D'Arcangelo for their technical help; Serge Mostowy for microscopy support; Thibaut Leger and Camille Garcia at the Institut Jacques Monod proteomic facility, UMR7592, Universite Paris Diderot/CNRS, for mass spectrometry analysis; Despoina A.I. Mavridou and R. Christopher D. Furniss (CMBI, Imperial College London) for E. coli MC1000 strains; Suzana P. Salcedo (IBCP, Lyon) for A. baylyi ADP1; and Gad Frankel (CMBI, Imperial College London) for S. arizonae genomic DNA. T.E.W. and S.A.H.are in receipt of PhD scholarships from the Wellcome Trust and Medical Research Council (MRC), respectively. E.M. is supported by MRC grant MR/N023250/1; L.M.N. is supported by MRC grant MR/N023250/1 and a Marie Curie Fellowship (PIIF-GA-2013-625318); N.P.B. is supported by a Canada Graduate Scholarship; H.C.L.Y. and W.V. are supported by Wellcome Trust grant 101824/Z/13/Z; A.H. is supported by H2020-MSCA-Global Fellowship grant 657766; R.D.H. is supported by MRC grant N000846/1; J.C.W. is supported by Canadian Institutes of Health Research (CIHR) grant PJT-156129; P.S.F. and A. Forster are supported by MRC grant MRK/K001930/1; and A. Filloux is supported by MRC grants MR/N023250/1 and MRK/K001930/1.