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How bacteria efficiently pack their bags?

Dr. Amitesh Anand, a chemistry graduate, earned his PhD in Chemical Biology from CSIR-Institute of Genomics and Integrative Biology (IGIB), India. He is currently a postdoctoral researcher in microbial systems and evolutionary biology with Prof. Bernhard Palsson at the University of California San Diego, USA. His research significantly contributes to understanding bacterial adaptive traits and stress response pathways. Starting June 2021, Dr. Anand will be setting up his research group at the Tata Institute of Fundamental Research (TIFR), Mumbai, India.

In this interview, Dr. Anand shares insights from his recent work titled: “Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications”
Published in Cell Reports (2021)


Author interview

How would you explain your paper’s key results to the non-scientific community?

We often think of bacteria only as harmful, but many are beneficial. These single-celled organisms must pack everything they need—both for growth and protection—into a small cellular space. It’s like packing for a trip with a small bag: you must balance between clothes for protection and food for energy. Similarly, bacteria must efficiently allocate their internal space between protective enzymes and growth-supporting metabolites.

In this study, we looked at what happens when this balance is disturbed.

We deleted a repressor gene that controls the production of the pyruvate dehydrogenase complex (a giant enzyme linking glycolysis to the TCA cycle) in E. coli. This led to overproduction of the enzyme, which took up too much space in the cell, disrupting balance and reducing growth.

Surprisingly, after 300 generations, the bacteria evolved a way to regain their growth. They did so by mutating the Shine-Dalgarno sequence (a ribosomal binding site), thereby fine-tuning the expression of this enzyme complex.


“This study further emphasizes the importance of examining the distal impact of any cellular perturbation.”


What are the possible consequences of these findings for your research area?

Classical microbiology often overlooks microbial adaptability across evolutionary timescales. This oversight limits our ability to combat infectious diseases and harness industrial microbes effectively. Our study not only reveals how bacteria restore gene expression without their usual regulators but also underscores the need to consider long-term adaptive responses when studying microbial physiology.


What was the exciting moment (eureka moment) during your research?

We suspected a mutation in the Shine-Dalgarno sequence was driving the improved growth. To test this, we engineered the same mutation into the original growth-retarded strain using CRISPR-Cas9. The strain’s growth improved dramatically—perfectly matching the evolved phenotype. That was our eureka moment.


What do you hope to do next?

After five rewarding years at UC San Diego, I am returning to India to establish my lab at TIFR Mumbai. My group will focus on the fundamental and translational aspects of cellular bioenergetics. I invite enthusiastic researchers to reach out if they’re interested in joining us.


Where do you seek scientific inspiration?

Inspiration is all around us—we are born scientists. It’s just that some people lose their scientific curiosity along the way.


How do you intend to help Indian science improve?

India holds vast potential. I hope to foster a nurturing research environment in my lab that inspires young minds to thrive and innovate.


Reference

Anand A, Olson CA, Sastry AV, Patel A, Szubin R, Yang L, Feist AM, Palsson BO.
Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications.
Cell Reports (2021) 35(1):108961. https://doi.org/10.1016/j.celrep.2021.108961

Edited by: Neha Varshney


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