Adaptive Mutagenesis at ebgR Is Regulated by PhoPQ

Adaptive mutations are mutations that occur in nondividing or very slowly dividing microbial cells during prolonged nonlethal selection and that are specific to the challenge of the selection in the sense that the only mutations that can be detected are those that provide a growth advantage to the cell. The phoPQ genes encode a two-component positively acting regulatory system that controls expression of at least 25 to 30 genes in Escherichia coli and Salmonella typhimurium. PhoPQ responds to a variety of environmental stress signals including Mg(2+) starvation and nutritional deprivation. Here I show that disruption of phoP or phoQ by Tn10dCam significantly reduces the adaptive mutation rate to ebgR, indicating that the adaptive mutagenesis machinery is regulated, directly or indirectly, by phoPQ. The finding that it is regulated implies that adaptive mutagenesis does not simply result from a failure of various error correction mechanisms during prolonged starvation.