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Researchers at the Indian Institute of Science (IISc), Bengaluru have discovered that Salmonella bacteria escapes host’s defences using two-pronged approach. Being one of the most common causes of food poisoning, India is facing the challenge of Non-typhoidal Salmonellae (NTS) which is rising at disturbing rates across India. It is reported that the inadequate surveillance of the infections in the country underestimates the prevalence rates.
According to the researchers from the Department of Microbiology and Cell Biology (MCB), IISc, Salmonella enterica, the disease-causing bacterium, uses various tactics to escape the human body’s defence mechanisms. In a new study, they highlighted two such strategies that the bacterium uses to protect itself, both driven by the same protein. The experiments were carried out on immune cell lines and immune cells extracted from mice models.
“When Salmonella enters the human body, each bacterial cell resides within a bubble-like structure known as Salmonella-containing vacuole (SCV). In response to the bacterial infection, the immune cells in the human body produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with pathways triggered to break down these SCVs and fuse them with cellular bodies called lysosomes or autophagosomes, which destroy the bacteria,” stated Dipshikha Chakravortty, Professor at MCB and corresponding author of the study.
However, these bacteria have developed robust mechanisms to maintain vacuolar integrity, which is crucial for their survival. For example, when a bacterial cell divides, the vacuole surrounding it also divides, enabling every new bacterial cell to be ensconced in a vacuole. This also ensures that more vacuoles are present than the number of lysosomes which can digest them, she said.
Medical experts are concerned on the prevalence of Salmonella infection across age-groups and attribute it to consumption of contaminated foods. While this calls for highest hygiene standards there is concern on the highest resistance of this bacteria against ampicillin and third generation cephalosporins which are the drugs of choice for treatment.
In the study published in Microbes and Infection, the IISc team reasoned that a critical protein produced by Salmonella, known as SopB, prevents both the fusion of SCV with lysosomes as well as the production of lysosomes, in a two-pronged approach to protect the bacterium. “It gives the upper hand to bacteria to survive inside other host cells,” said Dr Chatterjee.
A previous study from the same team had reported that the number of lysosomes produced by the host cells decreases upon infection with Salmonella. The researchers also found that mutant bacteria that were unable to produce SopB were also unable to reduce host lysosome numbers. Therefore, they decided to look more closely at the role that SopB was playing in the production of lysosomes, using advanced imaging techniques.
What they found was that SopB prevents the translocation of a critical molecule called Transcription Factor EB (TFEB) from the cytoplasm of the host cell into the nucleus. This translocation is vital because TFEB acts as a master regulator of lysosome production.
The researchers suggest that using small molecule inhibitors against SopB or activators of TFEB can help counter Salmonella infection. In subsequent studies, the team plans to explore the role of another host protein called Syntaxin-17 whose levels also reduce during Salmonella infection, said Chakravortty.
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