Multidrug resistance

 

The management of infectious diseases as well as cancer treatment is greatly complicated by the multidrug resistance mechanisms that enable cells to extrude a large number of drugs. We have been studying the EmrAB pump of E. coli, which can extrude a variety of chemically unrelated drugs and antibiotics. We showed that the pump is negatively regulated by the product of one of its own genes, namely emrR. We purified the EmrR protein and showed that it binds to the promoter of the operon, shutting it off. Furthermore, a large number of chemically unrelated compounds (that are both inducers and substrates for the pump) react with EmrR, rendering it unable to bind to the operator. Current work in this area is focused mainly on bacterial biofilms.

In more recent studies (in preparation), we have implicated an MDR pump in eurpathogenic E. coli biofilm resistance. See section on biofilms.

Xiong, A. A. Gottman, C. Park, M. Baetens, S. Pandza, and A. Matin. 2000. The EmrR protein represses the Escherichia coli emrRAB multidrug resistance operon by directly binding to its promoter region. In press, Antimicrobial Agents and Chemotherapy. [PDF]

Lomovskaya, O., K. Lewis, and A. Matin. 1995. EmrR is a negative regulator of the Escherichia coli Multidrug Resistance Pump EmrAB. Journal of Bacteriology, 177:2328-2344. [PDF]