Multidrug resistance in lactic acid bacteria: molecular mechanisms and clinical relevance

The active extrusion of cytotoxic compounds from the cell by multidrug tran sporters is one of the major causes of failure of chemotherapeutic treatmen t of tumor cells and of infections by pathogenic microorganisms. The second ary multidrug transporter LmrP and the ATP-binding cassette (ABC) type mult idrug transporter LmrA in Lactococcus lactis are representatives of the two major classes of multidrug transporters found in pro- and eukaryotic organ isms. Therefore, knowledge of the molecular properties of LmrP and LmrA wil l have a wide significance for multidrug transporters in all living cells, and may enable the development of specific inhibitors and of new drugs whic h circumvent the action of multidrug transporters. Interestingly, LmrP and LmrA are transport proteins with very different protein structures, which u se different mechanisms of energy coupling to transport drugs out of the ce ll. Surprisingly, both proteins have overlapping specificities for drugs, a re inhibited by the same set of modulators, and transport drugs via a simil ar transport mechanism. The structure-function relationships that dictate d rug recognition and transport by LmrP and LmrA will represent an intriguing new area of research.