T6SS-PSEUDO-LIP SIGNED
Type VI-dependent Pseudomonas aeruginosa phospholipases and host manipulation
Total Cost €
0EC-Contrib. €
0Partnership
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Project "T6SS-PSEUDO-LIP" data sheet
The following table provides information about the project.
| Coordinator |
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 1 | IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE | UK (LONDON) | coordinator | 195˙454.00 |
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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 |
|---|---|---|---|
| 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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