PLoS Pathogens | |
Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication | |
Subhash B. Arya1  Amit Tuli1  Divya Jagga2  Mahak Sharma2  Aastha Sindhwani2  Harmeet Kaur2  | |
[1] CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India;Department of Biological Sciences, Indian Institute of Science Education and Research Mohali (IISERM), Punjab, India | |
关键词: Salmonella; Salmonellosis; HeLa cells; Lysosomes; Small interfering RNAs; Salmonella typhimurium; Endosomes; Membrane fusion; | |
DOI : 10.1371/journal.ppat.1006700 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and lysosomes of the host cells in the form of interconnected network of tubules (Salmonella-induced filaments or SIFs), Salmonella gains access to both membrane and fluid-phase cargo from these compartments. This is essential for maintaining SCV membrane integrity and for bacterial intravacuolar nutrition. Here, we have identified the multisubunit lysosomal tethering factor—HOPS (HOmotypic fusion and Protein Sorting) complex as a crucial host factor facilitating delivery of late endosomal and lysosomal content to SCVs, providing membrane for SIF formation, and nutrients for intravacuolar bacterial replication. Accordingly, depletion of HOPS subunits significantly reduced the bacterial load in non-phagocytic and phagocytic cells as well as in a mouse model of Salmonella infection. We found that Salmonella effector SifA in complex with its binding partner; SKIP, interacts with HOPS subunit Vps39 and mediates recruitment of this tethering factor to SCV compartments. The lysosomal small GTPase Arl8b that binds to, and promotes membrane localization of Vps41 (and other HOPS subunits) was also required for HOPS recruitment to SCVs and SIFs. Our findings suggest that Salmonella recruits the host late endosomal and lysosomal membrane fusion machinery to its vacuolar niche for access to host membrane and nutrients, ensuring its intracellular survival and replication.
【 授权许可】
CC BY
【 预 览 】
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