Biology subjects

Nandy, P.

Publications and source records attributed to Nandy, P..

4 recordsLinked to original sources

bioRxiv2025

In vivo efficacy of L-ascorbic acid in restricting cholera pathogenesis

In the last three centuries, our world has experienced seven cholera pandemics. Cholera is a deadly diarrheal disease caused by Vibrio cholerae, an important member of the gamma-proteobacteria. Despite conventional treatments like antibiotics, vaccines, and ORS, the 7th cholera pandemic is still a major threat to developing nations. L-ascorbic acid was recently shown to effectively kill the Vibrio cholerae cells in vitro under various growth conditions mimicking the in vivo host conditions, including growth in the presence of bile salts, growth of acid-adapted V. cholerae, and growth in the presence of various ORS components. In the current study, we extend this work and test the efficacy of L-ascorbic acid in animal models (rabbit ileal loop and the removable intestinal tie adult rabbit diarrhea). We show that L-ascorbic acid can effectively reduce the bacterial load in both the rabbit models as well as fast-track the recovery from the diarrheal symptoms. ImportanceCholera is a severe human diarrheal disease that affects millions each year. Cholera treatment is primarily oral rehydration to balance the voluminous fluid loss. Previous studies have found that L-ascorbic acid (L-AA) is effective at inhibiting growth of Vibrio cholerae, the causative agent of cholera. Thus L-AA has potential as am inexpensive cholera therapeutic. Here, L-AA is tested in rabbit models to determine whether it can inhibit the effects of V. cholerae infection. Results suggest that L-AA treatment inhibits bacterial proliferation and leads to shortened recovery from disease.

microbiology↗

bioRxiv2022

Large-scale duplication events underpin population-level flexibility in bacterial tRNA gene copy number

The complement of tRNA genes within a genome is typically considered to be a (relatively) stable characteristic of an organism. Here we demonstrate that bacterial tRNA gene set composition can be more flexible than previously appreciated, particularly regarding tRNA gene copy number. We report the high-rate occurrence of spontaneous, large-scale, tandem duplication events in laboratory populations of the bacterium Pseudomonas fluorescens SBW25. The identified duplications are up to [~]1 Mb in size ([~]15 % of the wildtype genome) and are predicted to change the copy number of up to 917 genes, including several tRNA genes. The observed duplications are inherently unstable: they occur, and are subsequently lost, at extremely high rates. We propose that this unusually plastic type of mutation provides a mechanism by which tRNA gene set diversity can be rapidly generated, while simultaneously preserving the underlying tRNA gene set in the absence of continued selection. That is, if a tRNA set variant provides no fitness advantage, then high-rate segregation of the duplication ensures the maintenance of the original tRNA gene set. However, if a tRNA gene set variant is beneficial, the underlying duplication fragment(s) may persist for longer and provide raw material for further, more stable, evolutionary change.

evolutionary biology↗

bioRxiv2021

Adaptive strategies under prolonged starvation and role of slow growth in bacterial fitness

1.Adaptive evolution has the power to illuminate genetic mechanisms under a pre-defined set of selection factors in a controlled environment. Laboratory evolution of bacteria under long-term starvation has gained importance in recent years because of its ability to uncover adaptive strategies to overcome prolonged nutrient limitation- a condition thought to be encountered often by natural microbial isolates. In this evolutionary paradigm, bacteria are maintained in an energy-restricted environment in the growth phase called as long-term stationary phase or LTSP. This phase is characterized by a stable viable population size and highly dynamic genetic changes. Multiple independent iterations of LTSP evolution experiments have given rise to mutants that are slow-growing compared to the ancestor. Although the antagonistic regulation between rapid growth and stress response is fairly well-known in bacteria (especially Escherichia coli), the reason behind the growth deficit of many LTSP-adapted mutants has not been explored in detail. In this review, I revisit the trade-off between growth and stress response and delve into the regulatory mechanisms currently known to control growth under nutrient deficiency. Focusing on the theme of "sigma-factor competition" I try to search for the evolutionary reasoning of slow growth amongst mutants adapted to prolonged starvation. Additionally, I present novel experimental data indicating the dynamics of four such slow-growing variants that evolved during a 30-day long LTSP evolution experiment with Escherichia coli.

microbiology↗

bioRxiv2020

A mutant RNA polymerase activates the general stress response, enabling E. coli adaptation to late prolonged stationary phase

Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after three weeks o of maintaining an E. coli K12 population in stationary phase. This variant displayed a small colony phenotype, slow growth and was able to outcompete its ancestor over a narrow time window in stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously exposed to the antibiotic. We show that an RpoC (A494V) mutation confers the slow growth and small colony phenotype to this variant. The ability of this mutation to confer a growth advantage in stationary phase depends on the availability of the stationary phase sigma factor {sigma}S. The RpoC (A494V) mutation up-regulates the {sigma}S regulon. As shown over 20 years ago, early in prolonged stationary phase, {sigma}S attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance {sigma}S activity, either by mutating the gene for {sigma}S directly, or via mutations such as RpoC (A494V). The balance between the activities of the housekeeping major sigma factor and {sigma}S sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase. ImportanceAn important general mechanism of bacterial adaptation to its environment involves adjusting the balance between growing fast, and tolerating stresses. One paradigm where this plays out is in prolonged stationary phase: early studies showed that attenuation, but not complete elimination, of the general stress response enables early adaptation of the bacterium E. coli to the conditions established about 10 days into stationary phase. We show here that this balance is not static and that it is tilted back in favour of the general stress response about two weeks later. This can be established by direct mutations in the master regulator of the general stress response, or by mutations in the core RNA polymerase enzyme itself. These conditions can support the development of antibiotic tolerance though the bacterium is not exposed to the antibiotic. Further exploration of the growth-stress balance over the course of stationary phase will necessarily require a deeper understanding of the events in the extracellular milieu.

microbiology↗