How Salmonella manipulates host cell machinery to survive

– Creetika Dahal

Image: Umesh Chopra

Infection by the bacterium Salmonella enterica Typhi (S. Typhi) can lead to typhoid fever, a severe illness characterised by high fever, abdominal pain, and multi-organ involvement. Recently, researchers at IISc led by Dipshikha Chakravortty have uncovered a curious phenomenon that helps this bacterium fight off host response to infection.

Salmonella bacteria live in membrane-bound compartments called vacuoles within infected host cells. During bacterial division, these Salmonella-containing vacuoles (SCV) divide such that exactly one bacterium resides in each compartment. This allows the bacteria to increase the number of SCVs in the cell while decreasing the number of lysosomes (organelles found in the host cells), thereby protecting themselves from detection by the host cell.

To understand this phenomenon, the researchers zeroed in on the endoplasmic reticulum (ER) found in the host cell. When they altered the expression of proteins that affect the structure of the ER, bacterial proliferation altered drastically. In addition, 78% of the SCVs depended on the ER’s presence to divide. The team thus found that the host ER plays an essential role in managing SCV division.

The team also uncovered the role of a protein called SteA in SCV division. SteA sits on the vacuole membrane, and appears to help form membrane contact between the SCV and the ER. In lab culture experiments, cells infected with a genetically modified strain of Salmonella that could not produce SteA, the binding of SCVs to the ER dramatically reduced.

The scientists also noted that Salmonella could not maintain their one-bacterium-per-vacuole state in the absence of SteA, and formed bulky SCVs with multiple bacteria inside. These bulky SCVs were more easily detected and destroyed by the host cell, leading to a slower infection rate and reduced bacterial colonisation in the liver and spleen of lab mice.

The authors, therefore, suggest that targeting SteA and the link between SCVs and the ER can provide novel approaches to reducing Salmonella infection.

REFERENCE:
Chopra U, Bhansali P, Gangi Setty SR, Chakravortty D, Endoplasmic reticulum facilitates the coordinated division of Salmonella-containing vacuoles, mBio (2025).

https://doi.org/10.1128/mbio.00114-25

LAB WEBSITE:
https://mcb.iisc.ac.in/dclab/