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Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human Neutrophils.

Cell host & microbe | May 10, 2017

Neutrophils are the first line of defense against bacterial infections, and the generation of reactive oxygen species is a key part of their arsenal. Pathogens use detoxification systems to avoid the bactericidal effects of reactive oxygen species. Here we demonstrate that the Gram-negative pathogen Pseudomonas aeruginosa is susceptible to reactive oxygen species but actively blocks the reactive oxygen species burst using two type III secreted effector proteins, ExoS and ExoT. ExoS ADP-ribosylates Ras and prevents it from interacting with and activating phosphoinositol-3-kinase (PI3K), which is required to stimulate the phagocytic NADPH-oxidase that generates reactive oxygen species. ExoT also affects PI3K signaling via its ADP-ribosyltransferase activity but does not act directly on Ras. A non-ribosylatable version of Ras restores reactive oxygen species production and results in increased bacterial killing. These findings demonstrate that subversion of the host innate immune response requires ExoS-mediated ADP-ribosylation of Ras in neutrophils.

Pubmed ID: 28494242 RIS Download

Mesh terms: ADP Ribose Transferases | ADP-Ribosylation | Animals | Bacterial Toxins | Colony Count, Microbial | Epithelium | Eye | Female | GTPase-Activating Proteins | Humans | Immunity, Innate | Mice, Inbred C57BL | NADPH Oxidases | Neutrophils | Phagocytosis | Phosphatidylinositol 3-Kinases | Pseudomonas Infections | Pseudomonas aeruginosa | Reactive Oxygen Species | Signal Transduction | Survival Analysis | Type III Secretion Systems | ras Proteins

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Associated grants

  • Agency: NEI NIH HHS, Id: P30 EY011373
  • Agency: NEI NIH HHS, Id: R01 EY022052
  • Agency: NEI NIH HHS, Id: T32 EY007157
  • Agency: NEI NIH HHS, Id: R01 EY014362
  • Agency: NCATS NIH HHS, Id: UL1 TR001414

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