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Killing with proficiency: Integrated post-translational regulation of an offensive Type VI secretion system

Lookup NU author(s): Dr Giusy Mariano, Dr Julien Peltier, Professor Matthias Trost

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 Ostrowski et al. http://creativecommons.org/licenses/by/4.0/. The Type VI secretion system (T6SS) is widely used by bacterial pathogens as an effective weapon against bacterial competitors and is also deployed against host eukaryotic cells in some cases. It is a contractile nanomachine which delivers toxic effector proteins directly into target cells by dynamic cycles of assembly and firing. Bacterial cells adopt distinct post-translational regulatory strategies for deployment of the T6SS. ‘Defensive’ T6SSs assemble and fire in response to incoming attacks from aggressive neighbouring cells, and can utilise the Threonine Protein Phosphorylation (TPP) regulatory pathway to achieve this control. However, many T6SSs are ‘offensive’, firing at all-comers without the need for incoming attack or other cell contact-dependent signal. Post-translational control of the offensive mode has been less well defined but can utilise components of the same TPP pathway. Here, we used the anti-bacterial T6SS of Serratia marcescens to elucidate post-translational regulation of offensive T6SS deployment, using single-cell microscopy and genetic analyses. We show that the integration of the TPP pathway with the negative regulator TagF to control core T6SS machine assembly is conserved between offensive and defensive T6SSs. Signal-dependent PpkA-mediated phosphorylation of Fha is required to overcome inhibition of membrane complex assembly by TagF, whilst PppA-mediated dephosphorylation promotes spatial reorientation and efficient killing. In contrast, the upstream input of the TPP pathway defines regulatory strategy, with a new periplasmic regulator, RtkS, shown to interact with the PpkA kinase in S. marcescens. We propose a model whereby the opposing actions of the TPP pathway and TagF impose a delay on T6SS re-assembly after firing, providing an opportunity for spatial re-orientation of the T6SS in order to maximise the efficiency of competitor cell targeting. Our findings provide a better understanding of how bacterial cells deploy competitive weapons effectively, with implications for the structure and dynamics of varied polymicrobial communities.


Publication metadata

Author(s): Ostrowski A, Cianfanelli FR, Porter M, Mariano G, Peltier J, Wong JJ, Swedlow JR, Trost M, Coulthurst SJ

Publication type: Article

Publication status: Published

Journal: PLoS Pathogens

Year: 2018

Volume: 14

Issue: 7

Online publication date: 27/07/2018

Acceptance date: 17/07/2018

Date deposited: 20/08/2018

ISSN (print): 1553-7366

ISSN (electronic): 1553-7374

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.ppat.1007230

DOI: 10.1371/journal.ppat.1007230


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