Pseudomonas aeruginosa ExsA regulates a metalloprotease ImpA that inhibits phagocytosis of macrophages

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium whose type III secretion system (T3SS) plays a critical role in acute infections. Translocation of the T3SS effectors into host cells induces cytotoxicity. In addition, the T3SS promotes intracellular growth of P. aeruginosa during host infections. The T3SS regulon genes are regulated by an AraC-type regulator ExsA. In this study, we found that an extracellular metalloprotease encoded by impA (PA0572) is under the regulation of ExsA. An ExsA consensus binding sequence has been identified upstream of the impA gene and a direct binding of the site by ExsA was demonstrated via an electrophoretic mobility shift assay. We further demonstrate that the secreted ImpA cleaves the macrophage surface protein CD44, which inhibits phagocytosis of the bacterial cells by macrophages. In combination, our results reveal a novel ExsA regulated virulence factor that cooperatively inhibits the functions of macrophages with the T3SS.