Researchers at RGCB Discover New Methods to Overcome Bacterial Resistance to Antibiotics

THIRUVANANTHAPURAM: Researchers at the BRIC-Rajiv Gandhi Centre for Biotechnology (RGCB) have discovered that targeting the outer membrane of proteins, called porins, in pathogenic bacteria can significantly combat their resistance to antibiotics, which has emerged as one of the most serious global health threats.

Bacteria have evolved in several ways to block antibiotics, making once-effective drugs powerless. Their one key defence is through tiny protein channels in porins, which form channels to allow the entry of antibiotics. Reduction in the number of porins decreases the influx of drugs into bacteria, allowing them to develop resistance against different antibiotics and survive treatment.

The multidisciplinary investigation revealed the potential of targeting underexplored porins to combat antibiotic resistance.

The research work, which has been published in Small, a nanoscience & nanotechnology journal based in Weinheim (Germany), was carried out at Dr Mahendran’s lab at BRIC-Rajiv Gandhi Centre for Biotechnology (RGCB), in collaboration with Dr Arumugam Rajavelu’s lab at Indian Institute of Technology Madras, and Dr Jagannath Mondal’s lab at Tata Institute of Fundamental Research (TIFR), Hyderabad,

The researchers identified a dynamic porin CymAKp in the WHO-listed high-priority pathogen Klebsiella pneumonia. Using cutting-edge biophysical channel recordings and computer simulations, they discovered that CymAKp is specially adapted to allow cyclic sugars into the cell.

Building on this, they identified a clever way to use this pathway to sneak antibiotics in. It was found that certain antibiotics, called aminoglycosides, resemble cyclic sugars and can travel through CymAKp to enter the bacteria.

By understanding how these drugs interact with the porins, the research work revealed a promising new route to overcome resistance and make antibiotics more effective.

While many studies have explored porins in non-pathogenic bacteria, the roles of porins in clinically significant pathogens, particularly the ESKAPE group, remain under-investigated.

“By understanding and exploiting the molecular details of antibiotic transport through CymAKp, we pave the way for developing next-generation therapeutics designed to outsmart resistant pathogens,” they said.

RGCB Director Prof. Chandrabhas Narayana said the bacterial resistance to antibiotics has become a major challenge for the global medical community, especially for pharmacologists.

“Viewed in this backdrop, the current multidisciplinary research work will open up exciting possibilities for dealing with this challenge and making antibiotics more lethal and effective against bacterial infections through targeted antibiotics transport,“ he noted

The research work was funded by Department of Biotechnology, Govt of India; Anusandhan National Research Foundation (ANRF), Department of Science and Technology, Govt of India, and RGCB’s intramural funding.