Adaptive mutations are mutations that occur in nondividing or very slo
wly 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 growt
h advantage to the cell. The phoPQ genes encode a two-component positi
vely acting regulatory system that controls expression of at least 25
to 30 genes in Escherichia coli and Salmonella typhimurium, PhoPQ resp
onds to a variety of environmental stress signals including Mg2+ starv
ation 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 regulat
ed, directly or indirectly, by phoPQ, The finding that it is regulated
implies that adaptive mutagenesis does not simply result from a failu
re of various error correction mechanisms during prolonged starvation.