Multidrug efflux transporters

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Kmlwich TA, Lewinson O, Padan E, Bibi E. Do physiological roles foster persistence of drug/multidrug-efflux transporters A case study. Nat. Rev. Microbiol. 2005 3 566-572. 

Seelig A, Gatlik-Landwojtowicz E. Inhibitors of multidrug efflux transporters Their membrane and protein interactions. Minirev Med Chem 2005 5 135-51. 

Tikhonova, E.B., Wang, Q., and Zgurskaya, H.L (2002) Chimeric analysis of the multicomponent multidrug efflux transporters from Gram-negative bacteria. Journal of Bacteriology, 184 (23), 6499-6507. 

Aires, J.R. and Nikaido, H. (2005) Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli. Journal of Bacteriology,... 

Calabrese, D., Bille, J., and Sanglard, D. (2000) A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans FLIJI) conferring resistance to fluconazole. MicrobioJogy 146 (Pt 11), 2743-2754. 

Modulators and inhibitors of multidrug efflux transporters, such as Pgp, are used to reduce or inhibit MDR, which leads to a failure of the chemotherapy of, for example, cancers, epilepsy, bacterial, parasitic, and fungal diseases. Binding and transport of first-, second-, and third-generation modulators and inhibitors of Pgp take into account the properties of the drug (H-bonding potential, dimensions, and pK values) as well as the properties of the membrane. 

These proteins are encoded in chromosomal genes, but an RND protein recently was found encoded in a plasmid. These transporters serve as antiporters and have been shovm to be important in acquired and intrinsic resistance in gram-negative bacteria. All RND described thus far serve as multidrug efflux transporters. 

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