T6SS-PSEUDO-LIPProject ID: 654909
Financé au titre de:
Type VI-dependent Pseudomonas aeruginosa phospholipases and host manipulation
Détails concernant le projet
Coût total:EUR 195 454,80
Contribution de l'UE:EUR 195 454,80
Coordonné à/au(x)/en:United Kingdom
Appel à propositions:H2020-MSCA-IF-2014See other projects for this call
Régime de financement:MSCA-IF-EF-ST - Standard EF
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.
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.
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.
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.
Contribution de l'UE: EUR 195 454,80
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON