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

• Published in: bioRxiv
• Main Authors: Nandy, Pabitra, Chib, Savita, Aswin Sai Narain Seshasayee
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 28.01.2020
• Subjects: Antibiotics; Colonies; DNA-directed RNA polymerase; E coli; Genotypes; Mutants; Mutation; Phenotypes; RNA polymerase; Sigma factor; Stationary phase; β-Lactam antibiotics
• DOI: 10.1101/2020.01.27.922484

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 σS. The RpoC (A494V) mutation up-regulates the σS regulon. As shown over 20 years ago, early in prolonged stationary phase, σS attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance σS activity, either by mutating the gene for σS directly, or via mutations such as RpoC (A494V). The balance between the activities of the housekeeping major sigma factor and σS sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase.