Sigma Factor Competition in Escherichia Coli : Kinetic and Thermodynamic Perspectives

2022

Microbiology

The study of adaptive microbial evolution in the laboratory can illuminate the genetic mechanisms of gaining fitness under a pre-defined set of selection factors. Laboratory evolution of bacteria under long-term starvation has gained importance in recent years because of its ability to uncover adaptive strategies that overcome prolonged nutrient limitation, a condition often encountered by natural microbes. In this evolutionary paradigm, bacteria are maintained in an energy-restricted environment in a growth phase called long-term stationary phase (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 the stress response is well-known in bacteria (especially Escherichia coli ), the growth deficit of many LTSP-adapted mutants has not been explored in detail. In this review, I pinpoint the trade-off between growth and stress response as a dominant driver of evolutionary strategies under prolonged starvation. Focusing on mainly E. coli -based research, I discuss the various affectors and regulators of the competition between sigma factors to occupy their targets on the genome, and assess its effect on growth advantage in stationary phase (GASP). Finally, I comment on some crucial issues that hinder the progress of the field, including identification of novel metabolites in nutrient-depleted media, and the importance of using multidisciplinary research to resolve them.

Section: Bacterial Growth Dynamics Under Prolonged Nutrient Limitationmentioning

confidence: 99%

Section: Bacterial Growth Dynamics Under Prolonged Nutrient Limitationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of sigma factor competition in bacterial adaptation under prolonged starvation

2022

Microbiology

A mutant RNA polymerase activates the general stress response, enablingE. coliadaptation to late prolonged stationary phase

Chib

Seshasayee

2020

Preprint

5Escherichia coli populations undergo repeated replacement of parental genotypes with fitter 6 variants deep in stationary phase. We isolated one such variant, which emerged after three weeks o 7 of maintaining an E. coli K12 population in stationary phase. This variant displayed a small colony 8 phenotype, slow growth and was able to outcompete its ancestor over a narrow time window in 9 stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously 10 exposed to the antibiotic. We show that an RpoC (A494V) mutation confers the slow growth and 11 small colony phenotype to this variant. The ability of this mutation to confer a growth advantage in 12 stationary phase depends on the availability of the stationary phase sigma factor σ S . The RpoC 13 (A494V) mutation up-regulates the σ S regulon. As shown over 20 years ago, early in prolonged 14 stationary phase, σ S attenuation, but not complete loss of activity, confers a fitness advantage. Our 15 study shows that later mutations enhance σ S activity, either by mutating the gene for σ S directly, or 16 via mutations such as RpoC (A494V). The balance between the activities of the housekeeping major 17 sigma factor and σ S sets up a trade-off between growth and stress tolerance, which is tuned 18 repeatedly during prolonged stationary phase. 19

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

2021

Preprint

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.