Syntaxin 3 SPI‐2 dependent crosstalk facilitates the division of Salmonella containing vacuole

Abstract

Intracellular membrane fusion is mediated by membrane‐bridging complexes of soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Reports also suggest that Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. Salmonella containing vacuole (SCV) harbours recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis remains unclear. Upon knockdown of STX3, we observed a reduction in bacterial proliferation, which is concomitantly restored upon the overexpression of STX3. Live‐cell imaging of Salmonella‐infected cells showed that STX3 localises to the SCV membranes and thus might help in the fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found the interaction STX3‐SCV was abrogated when we infected with SPI‐2 encoded Type 3 secretion system (T3SS) apparatus mutant (STM ∆ssaV) but not with SPI‐1 encoded T3SS apparatus mutant (STM ∆invC). These observations were also consistent in the mice model of Salmonella infection. Together, these results shed light on the effector molecules secreted through T3SS encoded by SPI‐2, possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and help to maintain a single bacterium per vacuole.

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“…The SCV and infection-associated macro-pinosomes (IAMs) fuse with the help of SNARE proteins (SNAP25 and STX4) to maintain dynamic SCV growth and shrinkage . SPI-2 mediates the SCV division in a syntaxin 3-dependent manner to facilitate Salmonella survival . SipC recruits syntaxin 6, which helps acquire LAMP1 on SCV from the Golgi apparatus …”

“…191 SPI-2 mediates the SCV division in a syntaxin 3-dependent manner to facilitate Salmonella survival. 192 SipC recruits syntaxin 6, which helps acquire LAMP1 on SCV from the Golgi apparatus. 193 Salmonella can partially trigger autophagy in epithelial cells via SPI-1-encoded T3SS-1mediated damage to the SCV membrane, exposing the SCV lumen to various host cytoplasmic ubiquitin ligases.…”