Transcriptional regulation of multidrug efflux pumps in bacteria.

As integral membrane proteins demonstrating an extraordinarily wide substrate range, some degree of regulatory control over the expression of bacterial multidrug-resistance (MDR) transporters is to be expected. Excessive expression could be deleterious, due to direct, physical disruption of membrane integrity, or the unwanted export of essential metabolites, a potential side-effect of their broad substrate specificity. There are limited clues as to the physiological functions of most MDR transporters, but their expression is likely to be up-regulated in response to the presence of natural substrates of these pumps. Thus, it is no surprise that MDR genes are subject to regulation at the local level, consisting of examples of both transcriptional repression and activation by proteins encoded adjacent to that for the transporter. Furthermore, an increasing number of MDR genes have also been found to be controlled by global transcriptional activator proteins. Copyright 2001 Academic Press.