VE-Cadherin Cleavage by LasB Protease from Facilitates Type III Secretion System Toxicity in Endothelial Cells

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Pseudomonas aeruginosa (Pa) is a leading agent of nosocomial infections in humans, and clinical isolates are often multiresistant to antibiotics. As with most Gram-negative bacteria, Pa possesses a type III secretion system which consists of an injectisome through which the bacterium injects exotoxins inducing cytoskeleton collapse and apoptosis. Pa also delivers various toxins in the extracellular milieu by the type II secretion system, including the protease LasB. In order to disseminate throughout the body from the infection site and eventually reach the blood, the bacterium generally needs to cross the main barriers of the organism: the epithelium, the basal lamina and the vascular endothelium. Here we show that LasB specifically cleaves one main component of endothelial cell-to-cell junctions, the adhesive protein VE-cadherin, thus leading to junction disruption and endothelial barrier breakdown. VE-cadherin proteolysis also facilitates the action of type III exotoxins in endothelial cells. This cleavage mechanism is likely of major importance in Pa pathogenesis, as suggested by our bacterial dissemination experiments in mice.

Vyšlo v časopise: VE-Cadherin Cleavage by LasB Protease from Facilitates Type III Secretion System Toxicity in Endothelial Cells. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003939
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003939

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