Obiettivo Pseudomonas aeruginosa is a human pathogen causing life-threatening nosocomial infections. Its virulence mechanisms are pleiotropic, but secretion systems have a key role in transporting effectors, toxins and other virulence factors from the bacteria into the environment or target host cells. In recent years, a novel secretion system, the Type VI secretion system (T6SS), was shown to be important for P. aeruginosa virulence. Of three T6SSs encoded on the P. aeruginosa genome, the H1-T6SS is important for P. aeruginosa to compete with other bacteria and to establish chronic infections. H1-T6SS is involved in the secretion of at least three bacteriolytic effectors, Tse1-3, whereas no effectors have been identified for H2- and H3-T6SS. We hypothesise that proteins secreted by these two systems mediate other important aspects of P. aeruginosa virulence and their identification and characterisation are crucial to further understanding the H2- and H3-T6SS function and P. aeruginosa pathogenesis. This project will identify these effectors, using three approaches: 1) identification of regulatory elements controlling H2- and H3-T6SS gene expression in order to up-regulate expression of the H2- or H3-T6SS clusters and other co-regulated genes; 2) analysis of H1-, H2- and H3-T6SS gene expression in biofilm conditions using flowcells; 3) identification of H2- and H3-T6SS secreted effector proteins via secretome analysis of strains that have up-regulated expression of H2 and H3-T6SS clusters. The discovery of these secreted factors will be a breakthrough, since only a very limited number of T6SS substrates have been identified. It will give new insights into P. aeruginosa virulence and could be exploited for development of new therapeutic options. Campo scientifico natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsgenomes Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2012-IIF - Marie Curie Action: "International Incoming Fellowships" Invito a presentare proposte FP7-PEOPLE-2012-IIF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IIF - International Incoming Fellowships (IIF) Coordinatore IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Contributo UE € 221 606,40 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Regno Unito Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Brooke Alasya (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato