THE LOCAL REPRESSOR ACRR PLAYS A MODULATING ROLE IN THE REGULATION OFACRAB GENES OF ESCHERICHIA-COLI BY GLOBAL STRESS SIGNALS

Genes acrAB encode a multidrug efflux pump in Escherichia coli. We hav e previously reported that transcription of acrAB is increased under g eneral stress conditions (i.e. 4% ethanol, 0.5 M NaCl, and the station ary phase in Luria-Bertani medium). In this study, lacZ transcriptiona l fusions and an in vitro gel mobility shift assay have been utilized to study the mechanisms governing the regulation of acrAB. We found th at a closely linked gene, acrR, encoded a repressor of acrAB. Neverthe less, the general stress conditions increased transcription of acrAB i n the absence of functional AcrR, and such conditions surprisingly inc reased the transcription of acrR even more strongly than that of acrAB . These results suggest that the general-stress-induced transcription of acrAB is primarily mediated by global regulatory pathway(s), and th at one major role of AcrR is to function as a specific secondary modul ator to fine tune the level of acrAB transcription and to prevent the unwanted overexpression of acrAB. To our knowledge, this represents a novel mechanism of regulating gene expression in E. coli. Evidence als o suggests that the up-regulation of acrAB expression under general st ress conditions is not likely to be mediated by the known global regul ators, such as MarA or SoxS, although elevated levels of these protein s were shown to increase the transcription of acrAB.