RhoB promotes Salmonella survival by regulating autophagy
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Salmonella enterica serovar Typhimurium manipulates cellular Rho GTPases for host cell invasion by effector protein translocation via the Type III Secretion System (T3SS). The two Guanine nucleotide exchange (GEF) mimicking factors SopE and –E2 and the inositol phosphate phosphatase (PiPase) SopB activate the Rho GTPases Rac1, Cdc42 and RhoA, thereby mediating bacterial invasion. S. Typhimurium lacking these three effector proteins are largely invasion-defective. Type III secretion is crucial for both early and later phases of the intracellular life of S. Typhimurium. Here we investigated whether and how the small GTPase RhoB, known to localize on endomembrane vesicles and at the invasion site of S. Typhimurium, contributes to bacterial invasion and to subsequent steps relevant for S. Typhimurium lifestyle. We show that RhoB is significantly upregulated within hours of Salmonella infection. This effect depends on the presence of the bacterial effector SopB, but does not require its phosphatase activity. Our data reveal that SopB and RhoB bind to each other, and that RhoB localizes on early phagosomes of intracellular S. Typhimurium. Whereas both SopB and RhoB promote intracellular survival of Salmonella, RhoB is specifically required for Salmonella-induced upregulation of autophagy.
Finally, in the absence of RhoB, vacuolar escape and cytosolic hyper-replication of S. Typhimurium is diminished. Our findings thus uncover a role for RhoB in Salmonella-induced autophagy, which supports intracellular survival of the bacterium and is promoted through a positive feedback loop by the Salmonella effector SopB.
Finally, in the absence of RhoB, vacuolar escape and cytosolic hyper-replication of S. Typhimurium is diminished. Our findings thus uncover a role for RhoB in Salmonella-induced autophagy, which supports intracellular survival of the bacterium and is promoted through a positive feedback loop by the Salmonella effector SopB.
Originalsprog | Engelsk |
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Artikelnummer | 151358 |
Tidsskrift | European Journal of Cell Biology |
Vol/bind | 102 |
Udgave nummer | 4 |
Antal sider | 17 |
ISSN | 0171-9335 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We are grateful to Lothar Gröbe for flow cytometry and FACS sorting. We thank Sonia Costa and Stefan Arens for the assistance with cloning. This work was supported by the Deutsche Forschungsgemeinschaft (to KR, individual grant RO 2414/8–1 ) and by the HGF impulse fund (to TEBS, grant W2/W3–066 ).
Publisher Copyright:
© 2023
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