Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication.

PLoS Pathogens
Aastha SindhwaniMahak Sharma

Abstract

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...Continue Reading

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Citations

Mar 30, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xavier MicheletMichael B Brenner
Oct 24, 2018·EMBO Reports·Daphne van Elsland, Jacques Neefjes
Feb 28, 2020·Molecular & Cellular Proteomics : MCP·Tatjana ReuterNicole Hansmeier
Feb 21, 2019·The Journal of Cell Biology·Nicole Infarinato
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Tatjana ReuterNicole Hansmeier
Mar 16, 2021·Frontiers in Immunology·Jenny A Nguyen, Robin M Yates
May 15, 2021·Wiley Interdisciplinary Reviews. RNA·Nils Schmerer, Leon N Schulte
May 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Srinivasan RamakrishnanRoberto Docampo
Jun 4, 2019·Microbiology Spectrum·Marcela De Souza Santos, Kim Orth
Jun 10, 2020·ACS Nano·Federico FenaroliLoris Rizzello

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Methods Mentioned

BETA
GTPases
GTPase
transmission electron microscopy
immunoprecipitation
transfection
co-IP
flow cytometry
two-hybrid
pulldown
pull down

Software Mentioned

Adobe Photoshop CS
FireWire
GraphPad
FlowJo
ImageJ
ZEISS
Prism
ZEN Pro

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