Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human Neutrophils

Publication date: 10 May 2017
Source:Cell Host & Microbe, Volume 21, Issue 5
Author(s): Chairut Vareechon, Stephanie Elizabeth Zmina, Mausita Karmakar, Eric Pearlman, Arne Rietsch
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.

Graphical abstract

Teaser

Reactive oxygen species (ROS) production by neutrophils is a key antimicrobial defense. Vareechon et al. show that two type III secreted effectors of Pseudomonas aeruginosa, ExoS and ExoT, independently block ROS production by neutrophils. ExoS ADP-ribosylates Ras, which prevents binding to PI3K, thereby blocking NADPH oxidase activation and ROS production.


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