Salmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric Gi proteins.
Thorsten BrinkVeronika LeissPeter SiegertDoris JehleJulia K EbnerCarsten SchwanAliaksei ShymanetsSebastian WieseBernd NürnbergMichael HenselKlaus AktoriesJoachim H C OrthPublished in: PLoS pathogens (2018)
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 Gαi family, resulting in persistent activation of the G protein. Gi activation inhibits cAMP production and stimulates PI3-kinase γ by Gαi-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 Gαi and, thereby, to loss of directed migration of dendritic cells.
Keyphrases
- listeria monocytogenes
- type iii
- dendritic cells
- escherichia coli
- regulatory t cells
- drug induced
- signaling pathway
- end stage renal disease
- protein kinase
- reactive oxygen species
- chronic kidney disease
- respiratory failure
- ejection fraction
- early onset
- liver failure
- tyrosine kinase
- cell cycle arrest
- risk assessment
- climate change
- high glucose
- prognostic factors
- cell death
- amino acid
- endothelial cells
- candida albicans
- acute respiratory distress syndrome
- staphylococcus aureus