In a breakthrough that could reshape fundamental understanding of bacterial biology, Indian scientists have helped overturn a long-standing textbook model explaining how bacteria switch their genes on and off.
A new study led by researchers from the Bose Institute, an autonomous institute under the Department of Science and Technology (DST), in collaboration with Rutgers University, challenges the widely accepted “sigma (σ) cycle” model of bacterial gene regulation that has dominated biology for nearly five decades.
The findings, published in the journal Proceedings of the National Academy of Sciences (PNAS), reveal that the sigma cycle – long believed to be a universal mechanism in bacteria – does not apply across all species.
For nearly 50 years, biology textbooks have described how bacteria initiate gene transcription with the help of sigma (σ) factors – proteins that bind to RNA polymerase to start transcription and then detach to allow the process to continue. This model was largely based on studies of the bacterial strain Escherichia coli and its σ70 factor.
However, the new study shows that in Bacillus subtilis, the principal transcription initiation factor, σA, remains bound to RNA polymerase throughout the transcription process rather than dissociating after initiation. Similarly, a modified version of the E. coli σ70 factor was also found to stay attached.
“Our work shows that in Bacillus subtilis, the σA factor stays attached to RNA polymerase all the way through the transcription process,” said Dr. Jayanta Mukhopadhyay, the corresponding author from the Bose Institute. “This fundamentally changes how we think about bacterial transcription and gene regulation.”
In contrast, the full-length E. coli σ70 factor behaves differently, detaching stochastically during the elongation phase of transcription.
The researchers used a combination of biochemical assays, chromatin immunoprecipitation, and fluorescence-based imaging to observe sigma factor behaviour in real time. Their results demonstrated that Bacillus subtilis σA and an E. coli σ70 variant lacking a specific segment known as 1.1 remain stably associated with transcription complexes.
“These findings provide compelling evidence that the long-accepted σ cycle does not apply to all bacteria,” said co-author Aniruddha Tewari of the Bose Institute. “It opens new avenues for understanding bacterial gene regulation and its evolution.”
The discovery could have far-reaching implications for microbiology and biotechnology. A deeper understanding of bacterial transcription mechanisms may help scientists design better antibiotics or regulatory inhibitors that block infection mechanisms.
It could also aid in engineering microorganisms to more efficiently produce biofuels, biodegradable plastics, and therapeutic compounds.
The study was authored by researchers from the Bose Institute and Rutgers University, including Aniruddha Tewary, Shreya Sengupta, Soumya Mukherjee, Nilanjana Hazra, and Jayanta Mukhopadhyay, along with collaborators Y. W. Ebright, R. H. Ebright, and Yon W. Ebright from the United States.
