Researchers at Kerala's Rajiv Gandhi Centre for Biotechnology discover method to target drug-resistance in bacteria
(RGCB) have discovered that targeting the outer membrane of proteins, called
, in pathogenic bacteria can significantly combat their resistance to antibiotics.
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The discovery assumes significance with resistance to antibiotics being one of the most serious global health threats.
According to the research, bacteria evolved in several ways to block antibiotics, making once-effective drugs powerless. Anti-biotics target bacteria cells by entering them through tiny protein channels in porins. A 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
, said a statement.
The research work, published in Small, a nanoscience and nanotechnology journal based in Weinheim, Germany, was carried out at Dr Mahendran's lab at 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
. 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
, resemble cyclic sugars and can travel through CymAKp to enter the bacteria, the statement added.
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"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," it said.
While many studies 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," the researchers said.
RGCB director Chandrabhas Narayana said bacterial resistance to antibiotics has become a major challenge for the global medical community, especially for pharmacologists.
"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 added.
The research was funded by the Centre's department of biotechnology, department of science and technology, Anusandhan National Research Foundation (ANRF) and RGCB's intramural funding.
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