ExoU

ExoU is a virulence effector protein produced by the bacterium Pseudomonas aeruginosa and delivered into host cells through the bacterium’s Type III secretion system. It is a potent cytotoxin with phospholipase A2–like activity that can disrupt cellular membranes and contribute to tissue damage.

The toxin is injected into host cells where its activity is controlled by a eukaryotic cofactor, notably ubiquitin or ubiquitin-conjugated proteins. Once activated, ExoU rapidly hydrolyzes membrane phospholipids, leading to cell lysis and necrosis. This rapid mode of action helps explain the association of ExoU with acute, severe infections.

Genetically, exoU is encoded on a pathogenicity island and is frequently found in strains carrying the PAPI-2 island, where it coexists with other Type III effectors. The presence of exoU is often used as a marker of high virulence and is regulated by the Type III secretion system regulatory network, including the transcriptional activator ExsA. In some lineages, strains carry exoU while other effectors are present or absent, highlighting genetic diversity among P. aeruginosa isolates.

Clinical significance is centered on the association between ExoU and worse patient outcomes. ExoU-positive strains are linked to severe acute infections such as pneumonia and bacteremia and are generally associated with higher morbidity and mortality in clinical studies. Understanding exoU status aids epidemiological tracking and can inform assessments of virulence in clinical isolates.

ExoU is one of the major Type III secreted virulence factors of P. aeruginosa, alongside ExoS, ExoT, and ExoY.