Salmonella Typhimurium effector Ssel inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric G(i) proteins
Autor(en): | Brink, Thorsten Leiss, Veronika Siegert, Peter Jehle, Doris Ebner, Julia K. Schwan, Carsten Shymanets, Aliaksei Wiese, Sebastian Nuernberg, Bernd Hensel, Michael Aktories, Klaus Orth, Joachim H. C. |
Stichwörter: | ACTIVATION; DENDRITIC CELLS; G-BETA-GAMMA; G-PROTEINS; III SECRETION; LYMPH-NODES; MICE; Microbiology; NEUTROPHIL CHEMOTAXIS; Parasitology; PASTEURELLA-MULTOCIDA TOXIN; RGS PROTEINS; Virology | Erscheinungsdatum: | 2018 | Herausgeber: | PUBLIC LIBRARY SCIENCE | Journal: | PLOS PATHOGENS | Volumen: | 14 | Ausgabe: | 8 | Zusammenfassung: | 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 Ssel, which is involved in control of systemic dissemination of S. Typhimurium. Ssel deamidates a specific glutamine residue of heterotrimeric G proteins of the G alpha(i) family, resulting in persistent activation of the G protein. G(i) activation inhibits cAMP production and stimulates P13-kinase gamma by G alpha(i)-released G beta gamma subunits, resulting in activation of survival pathways by phosphorylation of Akt and mTOR. Moreover, Ssel-induced deamidation leads to non-polarized activation of G alpha(i) and, thereby, to loss of directed migration of dendritic cells. |
ISSN: | 15537366 | DOI: | 10.1371/journal.ppat.1007248 |
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