Mumbai: Researchers at the Indian Institute of Technology Bombay (IIT Bombay) have developed a DNA-based strategy that can make drug-resistant bacteria responsive to antibiotics again.
Antibiotics are routinely used to treat illnesses ranging from pneumonia and tuberculosis to urinary tract and bloodstream infections, and to prevent infections during surgeries, organ transplants, and chemotherapy.
But their widespread and often indiscriminate use has led to the crisis of antimicrobial resistance.
Two recent studies from IIT Bombay, led by Prof Ruchi Anand and Prof P I Pradeepkumar of the Department of Chemistry, presented a strategy focused not on developing yet another antibiotic, but on protecting the ones that already exist.
The researchers used short DNA sequences to block the enzymes that help bacteria resist antibiotics.
“Given the long, expensive path from drug discovery to clinic, improving existing drugs may be a more practical route. We know its safety and effects over the years and can use existing resources,” said Prof Anand.
In the first study, the researchers focused on specially identified short strands of DNA known as aptamers.
Unlike the conventional drugs, aptamers are made up of nucleic acids, synthetically produced, relatively stable, and easier to modify.
While the DNA aptamers performed well in laboratory assays, their use inside bacteria remains challenging because DNA molecules administered alone are prone to nuclease degradation and often cannot easily cross bacterial membranes.
To address this, in the second study, researchers explored a liposome-based delivery system.
Liposomes are tiny bubble-like spheres made of fatty molecules arranged in a double layer, structurally similar to biological cell membranes.
“Synthesising DNA is relatively straightforward, and liposome formulations are already widely used in medicine. Stability can be further improved by chemical modifications at the DNA ends – strategies routinely used in nucleic acid therapeutics,” said Prof Anand.
In the future, if developed for therapeutic use, the aptamer could be given alongside existing antibiotics.
By blocking the resistance mechanism, the engineered aptamer could help restore the antibiotic’s effectiveness, though more research, including animal studies and pharmacokinetic analyses, is still needed.
“But the beauty of the approach lies in the fact that we can re-sensitise old antibiotics,” added Prof Anand.
