RhoB promotes Salmonella survival by regulating autophagy
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RhoB promotes Salmonella survival by regulating autophagy. / Kirchenwitz, Marco; Halfen, Jessica; von Peinen, Kristin; Prettin, Silvia; Kollasser, Jana; zur Lage, Susanne; Blankenfeldt, Wulf; Brakebusch, Cord; Rottner, Klemens; Steffen, Anika; Stradal, Theresia E.B.
In: European Journal of Cell Biology, Vol. 102, No. 4, 151358, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - RhoB promotes Salmonella survival by regulating autophagy
AU - Kirchenwitz, Marco
AU - Halfen, Jessica
AU - von Peinen, Kristin
AU - Prettin, Silvia
AU - Kollasser, Jana
AU - zur Lage, Susanne
AU - Blankenfeldt, Wulf
AU - Brakebusch, Cord
AU - Rottner, Klemens
AU - Steffen, Anika
AU - Stradal, Theresia E.B.
N1 - Publisher Copyright: © 2023
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Autophagy
KW - CRISPR/Cas9
KW - Rho GTPases
KW - RhoB
KW - Salmonella Typhimurium
KW - SopB
U2 - 10.1016/j.ejcb.2023.151358
DO - 10.1016/j.ejcb.2023.151358
M3 - Journal article
C2 - 37703749
AN - SCOPUS:85170662391
VL - 102
JO - Cytobiologie
JF - Cytobiologie
SN - 0724-5130
IS - 4
M1 - 151358
ER -
ID: 368249741