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T6SS-PSEUDO-LIP SIGNED

Type VI-dependent Pseudomonas aeruginosa phospholipases and host manipulation

Total Cost €

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EC-Contrib. €

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 Outcomes and results

 T6SS-PSEUDO-LIP project word cloud

Explore the words cloud of the T6SS-PSEUDO-LIP project. It provides you a very rough idea of what is the project "T6SS-PSEUDO-LIP" about.

diseases    introduction    upstream    contribution    isolates    vi    nosocomial    events    prevalence    join    pathogen    clusters    pldb    h1    encodes    internalization    mechanisms    overview    fundamental    validate    encoded    confirm    inhibitors    dissect    bacterial    dissected    dependent    trans    mediated    secretion    phagocytic    pi3k    infectious    pseudomonas    bacteria    pld    secretes    performed    model    infections    phosphorylation    vitro    strains    kingdom    vivo    respectively    elucidate    innovative    interaction    toxins    isolated    invasion    clinical    phospholipases    host    discovered    t6ss    competitors    tract    basic    expression    killing    akt    decipher    secreted    mutants    delivering    infection    downstream    environment    action    pa    cell    respiratory    t6sss    strategy    plda    signalling    activation    murine    link    instrumental    aeruginosa    laboratory    screened    originality    relevance    entry    performing    cells    effectors    h3    newly    assays    virulence    h2   

Project "T6SS-PSEUDO-LIP" data sheet

The following table provides information about the project.

Coordinator		 IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

contact info
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 Coordinator Country United Kingdom [UK]
 Project website http://www.imperial.ac.uk/mrc-centre-for-molecular-bacteriology-and-infection/research/research-groups/professor-alain-filloux/
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-02-01   to  2018-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 195˙454.00

Map

 Project objective

Introduction

Pseudomonas aeruginosa (Pa), a nosocomial pathogen, secretes a wide range of virulence factors. A recently described secretion pathway is the type VI secretion system (T6SS). Pa encodes three T6SSs, H1-, H2- and H3-T6SS. The best-characterized H1-T6SS is involved in delivering toxins into bacterial competitors.

State-of-the art

Two phospholipases (Pld), PldA and PldB secreted via H2- and H3-T6SS, respectively, were recently identified as trans-kingdom virulence effectors, triggering both killing of bacterial competitors and internalization into non-phagocytic cells. They are encoded within two distinct pld clusters that are not present in all Pa isolates.

Objectives

Our study should (i) decipher the prevalence of the two pld clusters among Pa isolates, (ii) elucidate the role of those Pld during in vivo infection, (iii) confirm the Pld contribution in the T6SS mediated entry, (iv) dissect the PI3K/Akt signalling pathway activation mediated by Pld during Pa entry.

Overview of the action

The aim is to link the fundamental study of new virulence factors with their relevance into clinical isolates.

Methods

Pa strains isolated from infection or environment will be screened for the expression of pld clusters. The role of PldA and PldB as virulence factor will be assessed using a murine model of respiratory tract infection. In vitro invasion assays will be performed to validate the role of PldA in the H2-T6SS-dependent entry in non-phagocytic cells. Upstream and downstream signalling events of Akt phosphorylation induced by PldA and PldB upon infection will be dissected by performing cell infections with mutants and specific inhibitors.

Originality and innovative aspects of the project

Bacteria-host interaction mechanisms are instrumental in the development of infectious diseases. Basic (host laboratory) and clinical (the applicant) research will join to characterize a newly discovered virulence strategy of Pa.

 Publications

year authors and title journal last update
List of publications.
2018 Laurent Dortet, Charlotte Lombardi, François Cretin, Andréa Dessen, Alain Filloux
Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome
published pages: 378-386, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0109-7 		Nature Microbiology 3/3 2019-06-13

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