Targeting the Type Three Secretion System in Pseudomonas aeruginosa

Abstract

The injectisome type three secretion system (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This bacterium is responsible for severe infections in immunosuppressed or cystic fibrosis patients and has become resistant to many antibiotics. Inhibitors of T3SS may therefore constitute an innovative therapeutic target. After a brief description of the T3SS and its regulation, this review presents strategies to inhibit T3SS-mediated toxicity and describes the main families of existing inhibitors. Over the past few years, 12 classes of small-molecule inhibitors and two types of antibody have been discovered and evaluated in vitro for their capacity to inhibit T3SS expression or function, and to protect host cells from T3SS-mediated cytotoxicity. While only one small molecule has been tested in vivo, a bifunctional antibody targeting both the translocation apparatus of the T3SS and a surface polysaccharide is currently in Phase II clinical trials.

Keywords: Pseudomonas aeruginosa; cytotoxicity; inflammasome activation; toxins; type three secretion system; virulence..