New strategy found to combat drug-resistant Salmonella | India News
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BENGALURU: Scientists at the Indian Institute of Science (IISc) have uncovered a novel approach to tackle the growing threat of drug-resistant Salmonella, the bacterium responsible for typhoid and other food-borne illnesses.
Their research, published in the journal Redox Biology, reveals how Salmonella exploits a key molecule called spermidine to shield itself against the body’s immune defences, IISc said Tuesday.
When Salmonella infects a host, it is engulfed by macrophages – immune cells that try to kill the bacteria by producing reactive oxygen and nitrogen species. However, the study found that Salmonella uses spermidine to protect its proteins from this oxidative stress. Crucially, the bacterium hijacks the host’s machinery to ramp up spermidine production.
Spermidine from both bacteria and the host acts like a robust weapon for Salmonella to safeguard against reactive oxygen species, Dipshikha Chakravortty, Professor, IISc Department of Microbiology and Cell Biology (MCB), says.
“Salmonella’s strategies to survive are par excellence. With an increase in antimicrobial resistance in Salmonella, it is just impossible to eradicate,” Chakravortty added.
Researchers discovered that an existing FDA-approved drug called D,L-alpha-difluoromethylornithine (DFMO) can deplete spermidine levels in the host by blocking key enzymes involved in its synthesis pathway. Tests in mice showed that DFMO made the mice more resilient to Salmonella infections.
“Since we are targeting the host machinery, and not the bacteria directly, it will not evolve genetically to develop resistance,” said Abhilash Vijay Nair, the study’s first author.
The researchers plan further studies to identify additional targets for disrupting spermidine production.
Their research, published in the journal Redox Biology, reveals how Salmonella exploits a key molecule called spermidine to shield itself against the body’s immune defences, IISc said Tuesday.
When Salmonella infects a host, it is engulfed by macrophages – immune cells that try to kill the bacteria by producing reactive oxygen and nitrogen species. However, the study found that Salmonella uses spermidine to protect its proteins from this oxidative stress. Crucially, the bacterium hijacks the host’s machinery to ramp up spermidine production.
Spermidine from both bacteria and the host acts like a robust weapon for Salmonella to safeguard against reactive oxygen species, Dipshikha Chakravortty, Professor, IISc Department of Microbiology and Cell Biology (MCB), says.
“Salmonella’s strategies to survive are par excellence. With an increase in antimicrobial resistance in Salmonella, it is just impossible to eradicate,” Chakravortty added.
Researchers discovered that an existing FDA-approved drug called D,L-alpha-difluoromethylornithine (DFMO) can deplete spermidine levels in the host by blocking key enzymes involved in its synthesis pathway. Tests in mice showed that DFMO made the mice more resilient to Salmonella infections.
“Since we are targeting the host machinery, and not the bacteria directly, it will not evolve genetically to develop resistance,” said Abhilash Vijay Nair, the study’s first author.
The researchers plan further studies to identify additional targets for disrupting spermidine production.
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