New Insights into Tuberculosis: How Bacteria Evade Antibiotics

A groundbreaking study from IIT Bombay has shed light on how Mycobacterium tuberculosis, the bacteria responsible for tuberculosis, evades antibiotic treatment by modifying its outer lipid layer. Despite advancements in antibiotics and vaccination, TB continues to be a major health crisis, particularly in India. The research reveals that dormant bacteria require significantly higher drug concentrations to be affected, indicating that their resistance is linked to their membrane structure rather than genetic mutations. This discovery opens new avenues for improving TB treatment strategies by potentially weakening the bacteria's defenses.

By Narendra Chaudhary Dec 3, 2025, 16:21 IST

Understanding Tuberculosis Resistance

New Delhi, Dec 3: A recent study led by researchers from the Indian Institute of Technology (IIT) Bombay has revealed that the bacteria Mycobacterium tuberculosis, responsible for tuberculosis (TB), can withstand antibiotic treatments by altering their outer lipid layer.

Despite the availability of effective antibiotics and extensive vaccination efforts, TB remains a significant global health threat, claiming lives worldwide.

In 2024, approximately 10.7 million individuals were diagnosed with TB, resulting in 1.23 million fatalities, with India reporting over 2.71 million cases, making it one of the most affected countries.

The findings, published in the journal Chemical Science, indicate that the bacteria's ability to resist drugs is linked to their membranes, which serve as protective barriers primarily composed of lipids.

The research team cultivated the bacteria under two conditions: one simulating active infection with rapid division and another mimicking a dormant state typical of latent infections.

Upon exposing the bacteria to four standard TB medications—rifabutin, moxifloxacin, amikacin, and clarithromycin—the researchers discovered that the concentration required to inhibit 50% of bacterial growth was significantly higher in dormant bacteria compared to those in the active phase.

According to Prof. Shobhna Kapoor from the Department of Chemistry at IIT-B, this indicates that the same drug effective in the early stages of TB would need to be administered at much greater concentrations to eliminate dormant TB cells. Notably, this resistance was not attributed to genetic mutations, which are typically responsible for antibiotic resistance.

The absence of mutations linked to antibiotic resistance suggests that the reduced sensitivity to drugs is more closely associated with the bacteria's dormant state and their membrane structure rather than genetic alterations.

The research team identified over 270 unique lipid molecules within the bacterial membranes, revealing distinct differences between active and dormant cells. Active bacteria exhibited loose, fluid membranes, while dormant bacteria had rigid, tightly organized structures, highlighting their defense mechanisms.

Prof. Kapoor noted that while TB research has traditionally focused on proteins, lipids have now been recognized as active participants in the bacteria's survival and drug resistance.

Furthermore, the study found that rifabutin could penetrate active cells easily but struggled to cross the outer membrane of dormant cells. The rigid outer layer acts as a primary barrier, serving as the bacteria's first line of defense.

To enhance the effectiveness of antibiotics, weakening the outer membrane could be a viable strategy. Prof. Kapoor suggested that even established drugs could regain efficacy when combined with agents that disrupt the outer membrane, thereby preventing the bacteria from developing permanent resistance.