Fresh insight into TB bacteria may help tackle drug resistance
A new study by scientists at Bose Institute, Kolkata, has challenged a long-standing understanding of how bacteria regulate gene expression, opening up new possibilities in the fight against tuberculosis (TB) and other bacterial infections.
Tuberculosis remains one of the world’s deadliest infectious diseases, with drug-resistant strains posing a growing global concern. The bacterium Mycobacterium tuberculosis survives inside the human body by tightly controlling its gene activity, especially under stressful conditions.
For decades, scientists believed in a model known as the “σ-cycle,” where a protein called sigma (σ) factor binds to RNA polymerase to initiate transcription and is then released once the process moves into the elongation stage. This mechanism was widely considered universal across bacteria.
However, the new study has overturned this assumption.
Researchers Dr. Jayanta Mukhopadhyay and Dr. N. Hazra found that in Mycobacterium tuberculosis, sigma factors do not behave uniformly. While some detach from RNA polymerase during transcription, others remain bound throughout the process.
The findings, published in the journal Nucleic Acids Research, show that the so-called universal σ-cycle does not apply to all bacterial systems.
The study examined three key sigma factors — σA, σE, and σF — each associated with different cellular functions. σA, which maintains basic cellular activity, and σE, linked to stress response, were observed to detach from RNA polymerase during transcription. In contrast, σF remained firmly attached even as transcription continued.
This suggests that the bacterium uses multiple strategies to regulate gene expression rather than relying on a single mechanism.
The continued association of σF with RNA polymerase points to a previously unknown way in which TB bacteria sustain the expression of genes needed for survival under stress.
Researchers say this discovery could help identify new drug targets. Instead of focusing only on enzyme active sites — where resistance often develops — future therapies could aim to disrupt critical protein interactions essential for bacterial survival.
The study used advanced biochemical and cellular techniques, including transcription assays, fluorescence measurements, protein interaction analysis, and in vivo validation methods.
