Indian researchers redefine bacterial gene mechanism, boosting antibiotic research

In a breakthrough that challenges a foundational concept in molecular biology, Indian scientists have helped overturn a 50-year-old model explaining how bacteria regulate their genes. The findings, published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS), could reshape scientific understanding of bacterial transcription and pave the way for improved antibiotics and bioengineering applications.

For decades, biology textbooks have described the “sigma (σ) cycle” as a universal mechanism governing bacterial gene activation. According to this long-accepted model, sigma factors bind to RNA polymerase to initiate transcription—the process by which genetic information is copied into RNA—and then detach to allow the transcription process to continue. The theory was largely based on studies of the bacterium Escherichia coli and its sigma factor, known as σ70.

However, researchers from the Bose Institute, an autonomous institute under the Department of Science and Technology (DST), Government of India, in collaboration with Rutgers University, have found that this mechanism is not universal. Their study reveals that in Bacillus subtilis, the primary transcription initiation factor, known as σA, does not detach after initiation. Instead, it remains bound to RNA polymerase throughout the entire transcription process. A modified version of the E. coli σ70 factor was also observed to remain attached, contradicting long-standing scientific belief.

“Our work shows that in Bacillus subtilis, the σA factor stays attached to RNA polymerase all the way through transcription,” said Dr. Jayanta Mukhopadhyay of the Bose Institute, the corresponding author of the study. “This fundamentally changes how we think about bacterial transcription and gene regulation.”

Using advanced techniques such as biochemical assays, chromatin immunoprecipitation and fluorescence-based imaging, the team tracked sigma factor behaviour in real time. While full-length E. coli σ70 was observed to detach randomly during transcription elongation, σA in Bacillus subtilis and a truncated version of E. coli σ70 lacking a specific segment called region 1.1 remained stably associated with the transcription complex.

Co-author Aniruddha Tewari from the Bose Institute said the findings challenge the long-held assumption that the sigma cycle applies uniformly across bacteria. “It opens new avenues for understanding bacterial gene regulation and its evolution,” he noted.

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Scientists say the discovery could have far-reaching implications. A revised understanding of transcription mechanisms may help researchers design more targeted antibiotics or regulatory inhibitors that block bacterial infection processes. It could also support efforts to engineer microorganisms capable of efficiently producing biofuels, biodegradable plastics and therapeutic compounds.

The study was conducted by researchers from the Bose Institute, including Aniruddha Tewari, Shreya Sengupta, Soumya Mukherjee and Nilanjana Hazra, along with collaborators Y.W. Ebright, R.H. Ebright and Jayanta Mukhopadhyay from Rutgers University, USA. The findings mark a significant contribution by Indian scientists to global molecular biology research.