Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs

Abstract

Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina) and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium). In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

The protective effects of nasal PcrV‐CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia

“…In contrast, nasal PcrV‐alum failed to induce effective immunity against P. aeruginosa . Although bacterial clearance from the infected lungs did not increase significantly in the mice vaccinated with PcrV‐CpG, blockade of the TTSS may have prevented acute cell death in the lungs and systemic inflammatory responses, likely contributing to an improved survival rate, as we have shown in our previous experiments using a rabbit infection model and an isogenic mutant of P. aeruginosa that lacks ExoU and ExoT secretion .…”

“…In the case of P. aeruginosa , four type III secretory toxins, ExoS, ExoT, ExoU and ExoY have been identified . Among them, ExoU, which has bacterial patatin‐like phospholipase A 2 activity , has been identified as the major cytotoxin that induces cell death in the lungs and fatal pathophysiology, such as bacteremia and sepsis . Therefore, blocking ExoU translocation has great potential for reducing lethal outcomes of P. aeruginosa pneumonia.…”

Co‐opting oxylipin signals in microbial disease

“…The most extensively characterised phospholipase A is ExoU in P. aeruginosa . ExoU, a patatin‐like phospholipase and cytotoxin, is injected through the Type III secretion system to the host cell (Anderson et al, ; Sato et al, ; Sawa et al, ). ExoU liberates AA from eukaryotic cell membrane, an activity required for its toxicity (Rabin & Hauser, ; Saliba et al, ).…”

Patatin‐like phospholipases in microbial infections with emerging roles in fatty acid metabolism and immune regulation by Apicomplexa

“…One of the best characterized PLP is ExoU in Pseudomonas aeruginosa (Phillips et al, 2003;Sato and Frank, 2004). ExoU is a cytotoxic effector protein secreted through the type III secretion system upon cellular contact (Sawa et al, 2016). Host ubiquitination is required to activate the PLA 2 activity of ExoU leading to destruction of infected cell membranes (Anderson et al, 2011(Anderson et al, , 2015.…”