Like thieves evading capture, pathogenic salmonella disrupts the host’s immune system – Times of India

BENGALURU: Like thieves who constantly find ways to evade capture, Salmonella enterica, a disease-causing bacterium, uses various tactics to evade the human body’s defense mechanisms, an Indian Institute of Science (IISc) ) studies have shown.
The new study, published in Microbes and Infection, by researchers from IISC’s Department of Microbiology and Cell biology (MCB), highlight two strategies that the bacterium uses to protect itself, both driven by the same Protein.
“When Salmonella enters the human body, each bacterial cell resides inside a bubble-like structure called a Salmonella-containing vacuole (SCV). In response to bacterial infection, immune cells in our body release reactive oxygen species (ROS). produce ROS) and Reactive nitrogen species (RNS), with pathways activated to break down these SCVs and fuse them with cellular bodies called lysosomes or autophagosomes, which destroy bacteria,” said IISc.
However, these bacteria have evolved robust mechanisms to maintain vacuolar integrity, which is crucial for their survival. “For example, when a bacterial cell divides, the space around it also divides, enabling each new bacterial cell to become enclosed in the space. This also ensures that “There are more vacuoles than the number of lysosomes that can digest them,” added IISc.
In the study, the team concluded that a key protein produced by Salmonella, known as SopB, is involved in a two-pronged approach to protecting the bacterium, along with the fusion of SCV with lysosomes. Inhibits both the production of lysosomes.
“This gives the bacteria an upper hand to survive inside macrophages or other host cells,” says Ritika Chatterjee, a former PhD student at MCB and first author of the study. These experiments were performed on immune cells derived from immune cell lines and mouse models.
SOPB acts as a phosphatase, helping to remove phosphate groups from phosphoinositide, a type of membrane lipid. SopB helps Salmonella alter the dynamics of the vacuole – specifically it changes the type of inositol phosphates in the vacuole membrane – which prevents the fusion of the vacuole with the lysosome.
“A previous study by the same team reported that the number of lysosomes produced by host cells is reduced following Salmonella infection… Mutant bacteria that were unable to produce SopB also showed reduced numbers of host lysosomes. were unable to. Therefore, they decided to look more closely at the role that SopB was playing in lysosome production, using advanced imaging techniques,” said IISc.
What they found was that SopB blocks the transport of an important molecule called transcription factor EB (TFEB) from the cytoplasm (the material inside a cell other than the nucleus) into the nucleus. This translocation is critical because TFEB acts as a master regulator of lysosome production.
“This is the first time we have considered that SopB can act in a dual manner,” the team said, noting that SOPB alters key dynamics of the SCV that affects the translocation of TFEB into the nucleus.
“While other groups have already reported the function of SopB in mediating invasion of epithelial cells, the novelty of our study lies in identifying the function of SopB in inhibiting vacuolar fusion with existing autophagosomes/lysosomes, and another mechanism Carr, which provides Salmonella. with a survival benefit by increasing the ratio of SCV to lysosomes,” says MCB professor and corresponding author of the study Deepshikha Chakraborty.
The researchers suggest that the use of small molecule inhibitors against the activators of SOPB or TFEB may help combat Salmonella infection.
In a later study, the team plans to explore the role of another host protein called syntaxin-17, whose levels also decrease during Salmonella infection. “How do SCVs reduce Syntaxin-17 levels? Do they replace it with some other molecule, or do the bacteria degrade it? We [plan to] Look forward to it,” says Chakraborty.

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