Salmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric Gi proteins

Thorsten Brink, Veronika Leiss, Peter Siegert, Doris Jehle, Julia K. Ebner, Carsten Schwan, Aliaksei Shymanets, Sebastian Wiese, Bernd Nürnberg, Michael Hensel, Klaus Aktories, Joachim H. C. Orth (+1 others)
2018 PLoS Pathogens  
Salmonella enterica serotype Typhimurium (S. Typhimurium) is one of the most frequent causes of food-borne illness in humans and usually associated with acute self-limiting gastroenteritis. However, in immunocompromised patients, the pathogen can disseminate and lead to severe systemic diseases. S. Typhimurium are facultative intracellular bacteria. For uptake and intracellular life, Salmonella translocate numerous effector proteins into host cells using two type-III secretion systems (T3SS),
more » ... ich are encoded within Salmonella pathogenicity islands 1 (SPI-1) and 2 (SPI-2). While SPI-1 effectors mainly promote initial invasion, SPI-2 effectors control intracellular survival and proliferation. Here, we elucidate the mode of action of Salmonella SPI-2 effector SseI, which is involved in control of systemic dissemination of S. Typhimurium. SseI deamidates a specific glutamine residue of heterotrimeric G proteins of the Gα i family, resulting in persistent activation of the G protein. G i activation inhibits cAMP production and stimulates PI3-kinase γ by Gα i -released Gβγ subunits, resulting in activation of survival pathways by phosphorylation of Akt and mTOR. Moreover, SseI-induced deamidation leads to non-polarized activation of Gα i and, thereby, to loss of directed migration of dendritic cells. Author summary Salmonella Typhimurium is one of the most common causes of gastroenteritis in humans. In immunocompromised patients, the pathogen can cause systemic infections. Crucial virulence factors are encoded on two Salmonella pathogenicity islands SPI-1 and SPI-2. While SPI-1 encodes virulence factors essential for host cell invasion, intracellular proliferation of the pathogen depends mainly on SPI-2 effectors. Here, we elucidate the mode PLOS Pathogens | https://doi.
doi:10.1371/journal.ppat.1007248 pmid:30102745 fatcat:jxmr742rtvhgddsyw3xeuumynq