Hypermutation in derepressed operons of Escherichia coli K12

This article presents evidence that starvation for leucine in an Escherichi a coli auxotroph triggers metabolic activities that specifically target the leu operon for derepression, increased rates of transcription, and mutatio n. Derepression of the leu operon was a prerequisite for its activation by the signal nucleotide, guanosine tetraphosphate, which accumulates in respo nse to nutritional stress (the stringent response). A quantitative correlat ion was established between leuB mRNA abundance and leuB(-) reversion rates . To further demonstrate that derepression increased mutation rates, the ch romosomal leu operon was placed under the control of the inducible tac prom oter. When the leu operon was induced by isopropyl-D-thiogalactoside, both leuB mRNA abundance and leuB- reversion rates increased. These investigatio ns suggest that guanosine tetraphosphate may contribute as much as attenuat ion in regulating leu operon expression and that higher rates of mutation a re specifically associated with the derepressed leu operan.