Authors: Mohamed F. Mohamed, Kajal Gupta, Josef W. Goldufsky, Ruchi Roy, Lauren T. Callaghan, Dawn M. Wetzel, Timothy M. Kuzel, Jochen Reiser, Sasha H. Shafikhani
Published: 2022-03-11
DOI: 10.1038/s41467-022-28967-5
Source: Full article
AbstractType 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, includingPseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressingP. aeruginosastrains. Here we show that T3SS recognition leads to a rapid phosphorylation cascade involving Abl / PKCĪ“ / NLRC4, which results in NLRC4 inflammasome activation, culminating in inflammatory responses that limitP. aeruginosainfection in wounds. We further show that ExoT functions as the main anti-inflammatory agent forP. aeruginosain that it blocks the phosphorylation cascade through Abl / PKCĪ“ / NLRC4 by targeting CrkII, which we further demonstrate to be important for Abl transactivation and NLRC4 inflammasome activation in response to T3SS andP. aeruginosainfection.