Salmonella trafficking is defined by continuous dynamic interactions with the endolysosomal system.

Area of Science:

• Cell Biology
• Microbiology
• Infectious Diseases

Background:

• Salmonella enterica invades non-phagocytic cells, residing in a Salmonella-containing vacuole (SCV).
• SCV biogenesis typically involves interactions with the host cell's endocytic pathway.
• Previously, it was thought Salmonella avoided fusion with terminal lysosomes to establish its niche.

Purpose of the Study:

• To re-evaluate the interaction between the SCV and the endocytic pathway.
• To investigate the mechanisms and extent of SCV fusion with late endosomes/lysosomes.
• To determine if SCV-lysosome fusion inhibition is critical for Salmonella replication.

Main Methods:

• High-resolution live-cell imaging.
• Tracking of content transfer and acidification within the SCV.
• Utilizing inhibitors for microtubules and vacuolar acidification.
• Investigating the role of the small GTPase Rab7.

Main Results:

• Detected direct transfer of late endosomal/lysosomal content into SCVs within 30 minutes of invasion.
• Observed SCV acidification and Rab7 involvement, similar to phagosome-lysosome fusion.
• Found SCVs exhibited delayed fusion and acidification compared to E. coli or heat-killed Salmonella vacuoles.
• Demonstrated that these delays were independent of type III secretion systems.

Conclusions:

• Salmonella-containing vacuoles interact extensively with the endocytic pathway, including fusion with late endosomes/lysosomes.
• Inhibition of SCV-lysosome fusion is not the primary mechanism for Salmonella establishing its replicative niche in epithelial cells.
• These findings necessitate a re-evaluation of Salmonella's intracellular survival strategies.