Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors,including several that function to interfere with host ubiquitin signaling.Although the mechanism of a...Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors,including several that function to interfere with host ubiquitin signaling.Although the mechanism of action of many such effectors has been elucidated,how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined.In this study,we found that the SPI‐2 effector SseK3 inhibits SNARE pairing to promote the formation of a Salmonella‐induced filament by Arg‐GlcNAcylation of SNARE proteins,including SNAP25,VAMP8,and Syntaxin.Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the E3 ubiquitin ligase TRIM32,which catalyzes K48‐linked ubiquitination on SseK3 and targets its membrane‐associated portion for degradation.Hence,TRIM32 antagonizes SNAP25 Arg‐GlcNAcylation induced by SseK3 to restrict Salmonella‐induced filament biogenesis and Salmonella replication.Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factors.展开更多
基金supported by the National Key Research and Development Programs of China(2021YFD1800404 and 2018YFA0508000)the National Natural Science Foundation of China(32270197 and 32200156)+1 种基金the Natural Science Foundation of Hubei Provincial Department of Education(D20222104 and Q20212106)the Hubei Provincial Natural Science Foundation(2021CFB472 and 2022CFB934).
文摘Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors,including several that function to interfere with host ubiquitin signaling.Although the mechanism of action of many such effectors has been elucidated,how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined.In this study,we found that the SPI‐2 effector SseK3 inhibits SNARE pairing to promote the formation of a Salmonella‐induced filament by Arg‐GlcNAcylation of SNARE proteins,including SNAP25,VAMP8,and Syntaxin.Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the E3 ubiquitin ligase TRIM32,which catalyzes K48‐linked ubiquitination on SseK3 and targets its membrane‐associated portion for degradation.Hence,TRIM32 antagonizes SNAP25 Arg‐GlcNAcylation induced by SseK3 to restrict Salmonella‐induced filament biogenesis and Salmonella replication.Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factors.
