A Type III Secretion Negative Clinical Strain of Pseudomonas aeruginosa Employs a Two-Partner Secreted Exolysin to Induce Hemorrhagic Pneumonia
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Summary

Virulence of Pseudomonas aeruginosa is typically attributed to its type III secretion system (T3SS). A taxonomic outlier, the P.聽aeruginosa PA7 strain, lacks a T3SS locus, and no virulence phenotype is聽attributed to PA7. We characterized a PA7-related, T3SS-negative P.聽aeruginosa strain, CLJ1, isolated from a patient with fatal hemorrhagic pneumonia. CLJ1 is highly virulent in mice, leading to lung hemorrhage and septicemia. CLJ1-infected primary endothelial cells display characteristics of membrane damage and permeabilization. Proteomic analysis of CLJ1 culture supernatants identified a hemolysin/hemagglutinin family pore-forming toxin, Exolysin (ExlA), that is exported via ExlB, representing a聽putative two-partner secretion system. A recombinant P.聽aeruginosa PAO1螖pscD::exlBA strain, deficient for T3SS but engineered to express ExlA, gained lytic capacity on endothelial cells and full virulence in mice, demonstrating that ExlA is necessary and sufficient for pathogenicity. This highlights clinically relevant T3SS-independent hypervirulence, isolates, and points to a broader P.聽aeruginosa pathogenic repertoire.

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