MUMBAI, Dec. 4 -- A new IIT-Bombay-Monash University study has found that tuberculosis (TB) bacteria survive antibiotic treatment by hardening their outer shell, making it difficult for drugs to penetrate. The research, published in the peer-reviewed journal Chemical Science on Wednesday, explains why dormant TB bacteria remain largely untouched during treatment and continue to persist for months despite medication. The study, led by Prof Shobhna Kapoor of IIT Bombay and Prof Marie-Isabel Aguilar of Monash University, Australia, tracked how the outer layer of the bacteria changes as they shift from active infection to a slow, dormant phase. "People have studied TB from the protein point of view for decades," said Kapoor. "But lipids (fatty substances that are insoluble in water) were long seen as passive components. We now know that they actively help the bacteria survive and resist drugs." India carries one of the world's highest TB burdens, including a large population with latent TB-individuals who have no symptoms but carry dormant bacteria that can become active if their immunity drops. Only a few diagnostic tools exist globally for latent TB, and none are available in the Indian market, making early detection difficult. Dormant TB bacteria cells multiply extremely slowly, and most antibiotics target only fast-growing bacteria. The study shows that dormant bacteria survive not because of genetic mutations, but because they change the structure of their outer coating. In this phase, the outer layer becomes packed with long, waxy fat-like molecules, forming a dense, rigid shell. This prevents TB drugs, specifically rifabutin, moxifloxacin, amikacin and clarithromycin, from entering the cell. Active bacteria, by contrast, have a looser coating that allows drugs to pass through. To study this phenomenon safely, researchers used mycobacterium smegmatis, a harmless cousin of TB bacteria, and grew it in two states: active and dormant. When exposed to the four drugs, the dormant cells required two to ten times higher doses to stop growth even though they had no resistance-causing mutations. This confirmed that the hardened outer layer, not genetic change, was blocking the drugs. Using mass spectrometry, the team compared the fats in the bacterial coats and found clear shifts. Active cells had more flexible fats while dormant cells had more waxy fats that created a tight barrier. Rifabutin could enter active cells easily but barely crossed into dormant ones. "The rigid outer layer becomes the main barrier. It is the bacterium's first and strongest line of defence," said Kapoor. Dr Sushant Mane, associate professor and nodal officer for paediatric TB at JJ Hospital's National Centre of Excellence for TB, who was not involved with the study, said, "They have tested dormant bacilli in the latent phase, where drugs do not act well. This concentration of lipids is a new finding. It is good lab-based work, but it needs validation in real TB bacteria and across different conditions before we can conclusively say it works. If researchers can combine existing drugs with molecules that improve penetration, it will help in treating latent TB." The researchers say that weakening the bacterium's outer shell could make existing antibiotics far more effective....