The Role of ExoS in Dissemination of during Pneumonia

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Dissemination to the bloodstream is a poor prognostic sign in patients with hospital-acquired pneumonia, yet the mechanism by which this occurs is poorly understood. To begin to address this issue, we have used a mouse model of P. aeruginosa pneumonia to study the mechanism by which the type-III-secreted effector protein ExoS enhances bacterial dissemination. We show that intoxication of type I pneumocytes by ExoS leads to cell death and disruption of the pulmonary-vascular barrier, allowing bacterial dissemination into the bloodstream. These effects required the ADP-ribosyltransferase activity of ExoS, as strains secreting an ExoS variant lacking this activity demonstrated reduced type I pneumocytes death and pulmonary-vascular breakdown. This study indicates that inhibitors of the ADP-ribosyltransferase activity of ExoS could serve as novel therapeutics for the prevention of bacteremic pneumonia.

Vyšlo v časopise: The Role of ExoS in Dissemination of during Pneumonia. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004945
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004945

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