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Abstract：
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.
摘要：
鼠伤寒沙门氏菌通过利用大量效应物为其复制创造了细胞内生态位，包括一些干扰宿主泛素信号的功能。尽管已经阐明了许多此类效应物的作用机制，宿主泛素网络和细菌毒力因子之间的相互作用在很大程度上决定了感染的结果仍然不明确.在这项研究中,我们发现SPI-2效应子SseK3抑制SNARE配对，通过SNARE蛋白的Arg-GlcNAcylation促进沙门氏菌诱导的细丝的形成，包括SNAP25、VAMP8和Syntaxin。进一步的研究表明，宿主细胞通过诱导E3泛素连接酶TRIM32的表达来抵消SseK3的活性，该酶催化SseK3上的K48连接的泛素化并靶向其膜相关部分进行降解。因此，TRIM32拮抗SseK3诱导的SNAP25Arg-GlcNAcylation，以限制沙门氏菌诱导的纤丝生物发生和沙门氏菌复制。我们的研究揭示了宿主细胞通过消除特定毒力因子来抑制细菌复制的机制。
