How bacteria efficiently pack their bags?

Dr. Amitesh Anand’s interview with Bio Patrika hosting “Vigyaan Patrika”, a series of author interviews. Dr. Anand, a chemistry graduate, earned his doctorate in Chemical Biology from CSIR-Institute of Genomics and Integrative Biology (IGIB), India. He is currently working on microbial systems and evolutionary biology with Prof. Bernhard Palsson at the University of California San Diego, USA. His research work has made significant contributions towards the understanding of bacterial adaptive features and their stress response pathways. He remains passionate about the microbial lifestyle and continues to explore pathogenic as well as applicative aspects of bacterial systems as a Postdoctoral employee. He is setting up his research group at the Tata Institute of Fundamental Research, Mumbai, India starting June 2021. Here, Dr. Anand talks about ‘how bacteria efficiently pack their bags’ and discusses his paper 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).

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

We mostly recognize bacteria as harmful pathogens, however, many of them are advantageous to us. Unlike us, these microorganisms can peculiarly maintain their lives as single-celled organisms. They have to pack various resources required for their growth as well as protection against environmental assaults within the restricted cell size. We can relate the dilemma of bacterial cell packing its resources to a similar situation that all of us experience during remote travel. We can call it a ‘Traveler’s bag packing dilemma’. The defined size of the bag allows us to carry a limited amount of resources. We have to carefully choose how much protective gear like clothes, shoes, etc. can be included so that we have sufficient space left to pack food items. Similarly, bacterial cells also have to carefully utilize their cellular space to pack enzymes and metabolites needed to support growth and protect them from environmental assaults. And, as expected, an imbalance in this resource partitioning compromises their growth potential. In this paper, we have examined the adaptive response of a bacterium to a resource imbalance.

Pyruvate dehydrogenase complex is a large enzyme complex linking glycolysis to the TCA cycle or Krebs cycle in the cell. We deleted the repressor of this enzyme complex from the Escherichia coli genome. As expected, the loss of repression resulted in the increased expression of this giant enzyme complex compromising the efficient packing of cellular volume and decreasing the growth rate of the bacterial strain. But the most interesting part of the study was the finding that the bacterial strain could regain its growth capabilities after about 300 generations of evolution. We have also examined the mechanistic basis of the observed adaptive changes in the strain. The evolved strains re-engineered the Shine-Dalgarno sequence of the Pyruvate dehydrogenase complex to tailor its expression. The details are discussed in the paper.

Figure 1: A schematic showing alternate strategies to regulate expression of the Pyruvate dehydrogenase 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?

Majority of the classical microbiological approaches fail to recognize the adaptive plasticity in the microbial physiology that is often manifested over an evolutionary timescale. This is one of the factors behind our limited success against the infectious agents and in realizing the full potential of industrially important strains. While revealing the mechanisms to restore gene expression in the absence of its canonical regulator, this study further emphasizes the importance of examining the distal impact of any cellular perturbation.

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

We were suspecting that a mutation in the Shine-Dalgarno sequence of the Pyruvate dehydrogenase gene could be responsible for the observed growth rate improvements. Therefore, we introduced this mutation in the growth retarded strain using CRISPR-Cas9 system. We were amazed to see the full recapitulation of the adaptive phenotype and this was definitely the eureka moment of the project.

What do you hope to do next?

After spending approximately five very productive years at the University of California San Diego, I am returning to India to set up my research group at the Tata Institute of Fundamental Research, Mumbai. My research group will focus on the fundamental and translational aspects of cellular bioenergetics. I encourage the readers of Bio Patrika to get in touch with me, if they are interested and looking for a research position in my group.

Where do you seek scientific inspiration?

My scientific inspiration comes from almost everywhere. We are born scientists; it is just that some of us lose the scientific temperament over time.

How do you intend to help Indian science improve?

Indian science has a huge potential and provides us with several opportunities. My intention is to create a nurturing environment in my research group and inspire young minds.

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 Rep. 2021 Apr 6;35(1):108961. doi: 10.1016/j.celrep.2021.108961.

Edited by: Neha Varshney

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