THE EXOENZYME-S REGULON OF PSEUDOMONAS-AERUGINOSA

Pseudomonas aeruginosa can cause severe life-threatening infections in which the bacterium disseminates rapidly from epithelial colonization sites to the bloodstream. In experimental models, the ability of P. a eruginosa to disseminate is linked to epithelial injury, in vitro cyto toxicity and expression of the exoenzyme S regulon. Using the expressi on of ExoS as a model, a series of genes that are important for regula tion, secretion and, perhaps, intoxication of eukaryotic cells have be en identified. Proteins encoded by the exoenzyme S regulon and the Yer sinia Yop virulon show a high level of amino acid homology, suggesting that P. aeruginosa may use a contact-mediated translocation mechanism to transfer anti-host factors directly into eukaryotic cells. Potenti al anti-host factors that may disrupt eukaryotic signal transduction t hrough ADP-ribosylation include ExoS and ExoT. Expression of ExoU, ano ther candidate anti-host factor, has been correlated with acute cytoto xicity and lung epithelial injury. Members of the exoenzyme S regulon represent only a portion of the virulence factor arsenal possessed by P. aeruginosa. It will be important to understand how the exoenzyme S regulon contributes to pathogenesis and whether these factors could se rve as potential therapeutic targets.