Targeting fatty coat of bacteria can make existing TB drugs more effective, say researchers

Mumbai, Dec 5 (PTI) Tuberculosis bacteria can resist antibiotics by altering the fatty outer layer of their cell wall, a study by researchers at the Indian Institute of Technology (IIT) Bombay and Monash University has found.

Targeting this outer membrane can make existing drugs against the disease more effective, the researchers suggested.

For more than a century, tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, has remained a serious global health problem.

In 2023 alone, about 10.8 million people became sick with TB, and 1.25 million died from it. India carries the largest burden, with over 2.6 million cases recorded in 2024.

A major challenge in controlling TB is the bacteria's ability to enter a latent or dormant phase soon after infection. During this stage, TB bacteria remain alive but metabolically quiet for years, producing no symptoms and unable to spread.

Yet, if the immune system becomes compromised due to HIV infection, some other illness or immunosuppressive drugs, these bacteria can resume activity.

Since most antibiotics kill only actively dividing TB cells, dormant bacteria that barely grow can withstand treatment and remain in the host, leading to antibiotic tolerance.

The new study under the guidance of Prof Shobhna Kapoor of the Department of Chemistry, IIT Bombay and Prof Marie-Isabel Aguilar of Monash University identifies how the bacteria survive antibiotic treatment and what contributes to their drug tolerance.

It also suggests that targeting this survival mechanism could make existing TB drugs more effective.

Building on existing knowledge, Prof Kapoor's team suspected that the key to the drug tolerance might lie in the bacteria's membranes -- complex barriers made mostly of fats, or lipids that protect the cell, the report said.

The concentration of drugs needed to stop 50 per cent of bacterial growth was two to ten times higher in dormant bacteria than in active ones.

"In other words, 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. This change was not caused by genetic mutations, which usually explain antibiotic resistance," said Prof Kapoor.

To check if the two bacterial phases have distinct lipid profiles, the researchers used advanced mass spectrometry to identify more than 270 distinct lipid molecules in the bacterial membranes.

"We found clear differences between the lipid profiles of active and dormant cells," Anjana Menon from Prof Kapoor's lab said.

If the outer membrane blocks antibiotics, weakening it could make the drugs work better, she said.

"Current TB treatment lasts at least six months, and dormant bacteria often survive this long course. Instead of only developing new antibiotics, we suggest improving existing ones. Even old drugs can work better if combined with a molecule that loosens the outer membrane," added Prof Kapoor.

This approach makes bacteria sensitive to the drugs again without giving them a chance to develop permanent resistance, she added. PTI SM KRK