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

Abstract

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