Grant: Project Grant

Pseudomonas aeruginosa is an important human pathogen that can cause serious complications in patients with burns, wounds, and immunocompromised diseases. P. aeruginosa is also a major cause for nosocomial infection and is a predominant pathogen in Cystic Fibrosis (CF) patients who suffer from chronic and polymicrobial lung infection. This proposal aims to understand how P. aeruginosa gains fitness during disease progression, and focuses on a deadly molecular weapon P. aeruginosa employs to kill competing species, i.e. the type VI secretion system (T6SS). P. aeruginosa possesses three independent T6SS systems (H1, H2 and H3). The T6SS shoots neighbouring cells with poisonous proteins. Our preliminary data show that CF sputum enhances the H1-T6SS activity within seconds of exposure. Extracellular DNA, commonly enriched in the CF lung, is responsible for such activation. Although several T6SS effectors are known, the complete set of H1, H2, and H3-T6SS-dependent effectors in P. aeruginosa have not been determined. My main objective is to understand the role of T6SS clusters in competitive fitness and virulence of P. aeruginosa. The T6SS-dependent key virulence effectors can be used as new drug targets to control P. aeruginosa infection.