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α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia


The pathogenic potentials of most microbes depend on a repertoire of virulence factors. Despite major progress in the understanding of the molecular mechanisms underlying the activities of bacterial effectors, little is known about how they cooperate during infection to overcome host immune defenses and promote microbial persistence. Here, we investigated the roles of two uropathogenic Escherichia coli (UPEC) effectors that are co-ordinately expressed, α-hemolysin (HlyA) and cytotoxic necrotizing factor 1 (CNF1). We demonstrated that the HlyA toxin is critical for bacterial stability in the blood and showed that one important role of HlyA is to inhibit the CNF1-induced host response. Collectively, these findings reveal why the coordinated activities of HlyA and CNF1 are necessary for the full virulence of UPEC. Moreover, they unravel a HlyA-driven counter-defense mechanism used by bacteria to facilitate their survival.


Vyšlo v časopise: α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004732
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004732

Souhrn

The pathogenic potentials of most microbes depend on a repertoire of virulence factors. Despite major progress in the understanding of the molecular mechanisms underlying the activities of bacterial effectors, little is known about how they cooperate during infection to overcome host immune defenses and promote microbial persistence. Here, we investigated the roles of two uropathogenic Escherichia coli (UPEC) effectors that are co-ordinately expressed, α-hemolysin (HlyA) and cytotoxic necrotizing factor 1 (CNF1). We demonstrated that the HlyA toxin is critical for bacterial stability in the blood and showed that one important role of HlyA is to inhibit the CNF1-induced host response. Collectively, these findings reveal why the coordinated activities of HlyA and CNF1 are necessary for the full virulence of UPEC. Moreover, they unravel a HlyA-driven counter-defense mechanism used by bacteria to facilitate their survival.


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