Open AccessSalmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric Gi proteins
Author(s) -
Thorsten Brink,
Veronika Leiss,
Peter Siegert,
Doris Jehle,
Julia K. Ebner,
Carsten Schwan,
Aliaksei Shymanets,
Sebastian Wiese,
Bernd Nürnberg,
Michael Hensel,
Klaus Aktories,
J. Orth
Publication year - 2018
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007248
Subject(s) - effector , salmonella enterica , heterotrimeric g protein , biology , intracellular parasite , salmonella , microbiology and biotechnology , deamidation , intracellular , type three secretion system , secretion , pi3k/akt/mtor pathway , signal transduction , g protein , bacteria , virulence , biochemistry , genetics , gene , enzyme
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), which 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.