A groundbreaking study by IIT Bombay has shed new light on how tuberculosis (TB) bacteria, specifically Mycobacterium tuberculosis, are able to resist antibiotics and survive for extended periods . The research indicates that these bacteria are not developing antibiotic resistance through typical genetic mutations, but rather by altering their outer fatty coating, or lipid membranes
TB remains a significant global health crisis, with 10.7 million people contracting the disease and 1.23 million succumbing to it in 2024 alone. India bears a substantial burden, reporting over 2.71 million cases in the same year
The IIT Bombay team, led by Professor Shobhna Kapoor from the Department of Chemistry, cultivated the bacteria in two distinct phases: an active, rapidly dividing phase akin to an active infection, and a dormant phase mimicking latent infections When exposed to common TB drugs like rifabutin, moxifloxacin, amikacin, and clarithromycin, dormant bacteria required significantly higher concentrations (two to ten times more) of these drugs to inhibit their growth compared to the active bacteria
“The same drug that worked well in the early stage of the disease would now be needed at a much higher concentration to kill the dormant/persistent TB cells,” explained Professor Kapoor. She emphasized that this reduced drug sensitivity was linked to the bacteria’s dormant state and their membrane coats, not genetic changes, which are typically associated with antibiotic resistance.
The study further identified over 270 different lipid molecules within the bacterial membranes, showcasing clear structural differences between active and dormant cells. Active bacteria exhibited loose, fluid membranes, while dormant ones possessed rigid, tightly ordered structures, suggesting a defensive mechanism.
Professor Kapoor highlighted that while proteins have been the focus of TB research for decades, lipids were often considered passive components. “We now know they actively help the bacteria survive and resist drugs,” she stated.
A key finding was that the antibiotic rifabutin could easily penetrate active cells but struggled to cross the outer membrane of dormant bacteria. “The rigid outer layer becomes the main barrier. It is the bacterium’s first and strongest line of defence,” Kapoor elaborated.
This discovery suggests a promising new approach to TB treatment. By weakening the outer membrane of the bacteria, even existing antibiotics could become more effective. “Even old drugs can work better if combined with a molecule that loosens the outer membrane,” said Kapoor, indicating that this strategy could resensitize bacteria to drugs without allowing them to develop permanent resistance.
-Rashmi Kumari
