Mycobacterium tuberculosis (Mtb), the microbe that causes tuberculosis (TB), actively reshapes its outer fat membrane to slip past immunity shields, survives stress and even rewires host cells to gain entry. A new study by the Indian Institute of Technology (IIT) Bombay, has found a way to detect these changes, which can help in understanding why TB bacteria are becoming increasingly multidrug-resistant.

The research led by Dr Shobhna Kapoor, Department of Biotechnology/Wellcome Trust India Alliance Intermediate Fellow at IIT-B, raises the possibility of spotting hard-to-diagnose infections by not just looking at proteins but fat. “The TB burden means a higher number of active TB patients in India. This is because of the relapse of the disease due to antimicrobial resistance (AMR), and finally non-compliance of patients to finish the required three-month therapy. This causes high rates of active, latent and drug-resistant infections, which are communicable,” she said.

Her work shows that the TB bacterium, which is rich in complex lipids, does not have a static membrane. It shifts as the bacterium moves between active and dormant states, helping it withstand stress, avoid detection and persist in the body for long periods.

“Our work also examines how TB bacteria alter the behaviour of the cells they infect,” Dr Kapoor said. The study, published in Journal of Materials Chemistry B, shows that these changes can be detected using a label-free method (which detects diseases without requiring external markers — such as dyes, fluorescent tags, or radioactive isotopes — for cell samples of TB) and liquid crystals, that change colour when cells change.

One reason TB is difficult to control is that the bacteria can enter a resting state called latent or dormant TB after the initial infection. They stay alive but are inactive, sometimes for many years. People with latent TB have no symptoms and cannot spread the disease. However, the bacteria can become active again if the immune system weakens, such as with another infection or HIV or use of immunosuppressants.

Most antibiotics work only on TB bacteria that are active and dividing; therefore, dormant TB cells, which grow very slowly or not at all, can survive treatment and persist in the infected person and even acquire antibiotic tolerance.

According to Dr Kapoor, cheap, fast and label-free diagnosis at an early stage is imperative. “Currently, standard tests include sputum-testing and culturing, followed by expensive immunological testing. We need cheaper, mass deployable diagnostic platforms without the need of cold storage transport and heavy equipment. Our study provides a proof of concept that label-free diagnosis platforms based on liquid crystals can differentiate between active and latent bacterial species relying on the subtle changes in their lipids. This obviates the need for expensive consumables and data analysis,” she added.

A second study led by Dr Kamakshi Sureka Paul, DBT/WT India Alliance Early Career Fellow at JIS Institute of Advanced Studies and Research, Kolkata, focuses on how the bacterium regulates itself. A key signalling molecule regulates growth and survival and researchers have introduced a tool to track these changes in real time inside living cells. The team has also identified compounds that disrupt this system, pointing to a new way of tackling TB. “We need to identify new therapeutic targets and develop alternative treatment strategies,” Dr Paul said.

The research team has focussed on a small bacterial signalling molecule that regulates processes essential for growth, survival, virulence, and host immune activation. “A novel class of inhibitors to disrupt this signalling system has been identified. This is a promising strategy for developing anti-virulence and antimicrobial therapies against TB,” Dr Paul explained.