Work

Endoplasmic reticulum facilitates the coordinated division of Salmonella -containing vacuoles

Year: 2025

Type: article

Abstract: ABSTRACT Salmonella Typhimurium (STM) resides in a membrane-bound compartment called the Salmonella -containing vacuole (SCV) in several infected cell types where bacterial and SCV division occur synchronously to maintain a single bacterium per vacuole. However, the mechanism behind this synchronous fission is not well understood. Fission of intracellular organelles is known to be regulated by the dynamic tubular endoplasmic reticulum (ER). In this study, we evaluated the role of ER in controlling SCV division. Interestingly, Salmonella -infected cells show activation of the unfolded protein response (UPR) and expansion of ER tubules. Altering the expression of ER morphology regulators, such as reticulon-4a (Rtn4a) and CLIMP63, significantly impacted bacterial proliferation, suggesting a potential role of tubular ER in facilitating SCV division. Live-cell imaging revealed the marking of tubular ER at the center of 78% of SCV division sites. This study also explored the role of SteA (a known Salmonella effector in modulating membrane dynamics) in coordinating the SCV division. SteA resides on the SCV membranes and helps form membrane contact between SCV and ER. The colocalization of ER with SCV enclosing STMΔ steA was significantly reduced, compared with SCV of STM WT or STMΔ steA:steA . STMΔ steA shows profound defects in SCV division, resulting in multiple bacteria in a single vacuole with proliferation defects. In vivo , the STMΔ steA shows a defect in colonization in the spleen and liver and affects the initial survival rate of mice. Overall, this study suggests a coordinated role of bacterial effector SteA in promoting ER contact/association with SCVs and regulating SCV division. IMPORTANCE This study highlights the essential role of the host endoplasmic reticulum in facilitating SCV division and maintaining a single bacterium per vacuole. The Salmonella effector SteA helps maintain the single bacterium per vacuole state. In the absence of SteA, Salmonella resides as multiple bacteria within a single large vacuole. The STMΔ steA shows reduced proliferation under in vitro conditions and exhibits colonization defects in vivo , highlighting the importance of this effector in Salmonella pathogenesis. These findings suggest that targeting SteA could provide a novel therapeutic approach to inhibit Salmonella pathogenicity.

Source: mBio

DOI: 10.1128/mbio.00114-25

Authors: Umesh Chopra, Priyanka Bhansali, Subba Rao Gangi Setty, Dipshikha Chakravortty

Institutions: Indian Institute of Science Bangalore, Indian Institute of Science Education and Research Thiruvananthapuram

Language: English

Topic: Salmonella and Campylobacter epidemiology

Subfield: Food Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,900