1887

Abstract

Multidrug resistance (MDR) in is due to the expression of the membrane ATP-binding cassette (ABC) transporter LmrCD. In the absence of drugs, the transcriptional regulator LmrR prevents expression of the operon by binding to its operator site. Through an autoregulatory mechanism LmrR also suppresses its own expression. Although the and genes have their own promoters, primer extension analysis showed the presence of a long transcript spanning the entire cluster, in addition to various shorter transcripts harbouring the genes only. ‘In-gel’ Cu-phenanthroline footprinting analysis indicated an extensive interaction between LmrR and the promoter/operator region. Atomic force microscopy imaging of the binding of LmrR to the control region of DNA showed severe deformations indicative of DNA wrapping and looping, while LmrR binding to a fragment containing the control region induced DNA bending. The results further suggest a drug-dependent regulation mechanism in which the genes are co-transcribed with as a polycistronic messenger. This leads to an LmrR-mediated regulation of expression that is exerted from two different locations and by distinct regulatory mechanisms.

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2011-05-01
2020-07-03
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