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

Area of Science:

• Cell Biology
• Microbiology
• Infectious Diseases

Background:

• Salmonella Typhimurium replicates within a specialized vacuole (SCV).
• SCV formation requires interaction with host late endosomes and lysosomes, forming Salmonella-induced filaments (SIFs).
• This interaction provides nutrients and membrane for SCV integrity.

Purpose of the Study:

• To identify host factors involved in SCV biogenesis and nutrient acquisition.
• To elucidate the mechanism by which Salmonella recruits host membrane compartments.

Main Methods:

• Depletion of host HOPS complex subunits.
• Investigated interactions between Salmonella effectors (SifA, SKIP) and host factors (HOPS, Arl8b).
• Assessed bacterial load in cell cultures and a mouse model.

Main Results:

• The HOmotypic fusion and Protein Sorting (HOPS) complex is essential for SCV development.
• HOPS facilitates the delivery of lysosomal content and membrane to SCVs, supporting SIF formation and bacterial nutrition.
• Salmonella effector SifA, with SKIP, recruits HOPS to SCVs, involving the GTPase Arl8b.

Conclusions:

• Salmonella actively recruits the host's endosomal-lysosomal fusion machinery (HOPS) to its vacuole.
• This recruitment enables Salmonella to access host membrane and nutrients for intracellular survival and replication.
• Targeting HOPS function presents a potential strategy to combat Salmonella infections.