Researchers at the Indian Institute of Science (IISc), Bengaluru have unlocked the mechanism by which Salmonella enterica, a bacterium that causes typhoid fever in humans, is able to shield itself from immune defences of the body.
The study could shed light on how to effectively treat and destroy the bacteria nicknamed ‘stealthy microbe’ due to its ability to evade the human immune system, making infections caused by it hard to treat.
In a study published in the journal of Microbes and Infection, scientists from the Department of Microbiology and Cell Biology (MCB) at IISc, highlighted a two-pronged approach that the Salmonella enterica bacterium uses to protect itself.
They identified a protein called SopB that is used by the bacterium to evade the host’s immune system and thereby survive and spread throughout the body.
Usually, cells have a mechanism to protect themselves from invading bacteria like Salmonella that enter the body in bubble-like structures called Salmonella containing vacuoles (SCV). In response to an invasion, immune cells break down the SCV and hand them over to lysosomes within cells that contain enzymes that destroy the bacteria.
However, the Salmonella bacteria have developed a way to maintain the integrity of this vacuole by producing an integral protein called SopB, which prevents the fusion of the SCV with lysosomes as well as the production of more lysosomes.
By using this two-pronged approach, the Salmonella bacteria was able to effectively evade the body’s defence system. “[This] gives the upper hand to bacteria to survive inside macrophages or other host cells,” explains Ritika Chatterjee, former PhD student at MCB and first author of the study.
A previous study by the same group showed that the number of lysosomes decreased in cells infected by Salmonella. On further investigation they realised that SopB was essential in the production of lysosomes in the body.
“The novelty of our study lies in identification of the function of SopB in inhibiting the vacuolar fusion with existing autophagosomes/lysosomes, and the second mechanism, which provides Salmonella with a survival advantage by increasing the ratio of SCV to lysosomes,” said Dipshikha Chakravortty, professor at MCB and corresponding author of the study.
The researchers hope that their findings can be used to develop potential targets to combat Salmonella infections in humans. By understanding how the bacterium evades the host’s immune system, it is possible to develop mechanisms to prevent its survival and spread in the host’s body, such as by using small molecule inhibitors against SopB to counter Salmonella infection, they said.
