The exoenzyme S regulon of Pseudomonas aeruginosa

Abstract

SummaryPseudomonas 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. aeruginosa to disseminate is linked to epithelial injury, in vitro cytotoxicity and expression of the exoenzyme S regulon. Using the expression of ExoS as a model, a series of genes that are important for regulation, secretion and, perhaps, intoxication of eukaryotic cells have been identified. Proteins encoded by the exoenzyme S regulon and the Yersinia 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. Potential anti-host factors that may disrupt eukaryotic signal transduction through ADPribosylation include ExoS and ExoT. Expression of ExoU, another candidate anti-host factor, has been correlated with acute cytotoxicity 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 serve as potential therapeutic targets.

Pseudomonas aeruginosa LecB Is Involved in Pilus Biogenesis and Protease IV Activity but Not in Adhesion to Respiratory Mucins

“…In addition, the mutants were assayed for phospholipase and exotoxin A secretion but found to be unaffected. Furthermore, no effect on the secretion of ExoS and ExoT, which are secreted through the type III secretion system (7,32), was observed in the lectin mutants.…”

Interactions between effector proteins of the Pseudomonas aeruginosa type III secretion system do not significantly affect several measures of disease severity in mammals

“…This opportunistic pathogen secretes four effector proteins: ExoS, ExoT, ExoU and ExoY (Frank, 1997). The enzymic and cell biological activities of these proteins are well defined.…”

Epigenesis and Dynamic Similarity in Two Regulatory Networks in Pseudomonas Aeruginosa

“…However, many mucoid bacteria isolated from the patient's lungs are also cytotoxic and therefore they are able to lyse the host's macrophages and thus overcome these defences (Dacheux et al, 2000(Dacheux et al, , 2001a. Cytotoxic P. aeruginosa, like many other cytotoxic bacteria synthesise a secretory apparatus (Type III) that enables them to inject toxins from their cytoplasm into the target cell (or in the medium when the contact is simulated by laboratory conditions such as Calcium depletion; Feltman et al, 2001;Franck, 1997). By contrast, most P. aeruginosa strains from the environment are not able to become cytotoxic in these conditions.…”

“…The regulatory networks responsible for the production and regulation of the proteins involved in Type III secretion have been studied in several bacterial pathogens (Hueck, 1998) including recently P. aeruginosa (Franck, 1997). Cytotoxicity is controlled by a main regulator, ExsA, which positively regulates in trans the expression of all the operons involved in the process, including its own, namely the production of the secretory apparatus and toxins (Dacheux et al, 2001b).…”