The mechanism of extrusion of cytotoxic compounds by p LmrP and LmrA has studied in whole cells, isolated im been membrane vesicles and mes. These studies revealed that the lipophilic substrates intercalate rapidly in the outer leaflet of the membrane. Subsequently, the sub strate flips over slowly to the leaflet from where it is inner picked up by LmrP LmrA and extruded in a proton motive or force ATP-dependent process to the external medium. or This vacuum-clcancr activity of LmrP and LmrA has subsequently been confirmed for P-glycoprotein. Recently, the role of LimrA in the resistance of L. lactis to antibiotics been studied. Expression of LmrA in has Escherichia coli confers this organism resistant to 17 out of the 21 clinically most used antibiotics, including antibiotics belonging to the classes of aminoglycosides cephalosporins, macrolides, penicillins, quinolones, strep- togramins and tetracyclins. Thus, mr has the broadest substrate specificity reported for MDRs In another LAB Iacobacilis brevis, a homolog of LmrA was found that confers resistance to the iso-alpha acids that are natural brewing process present in hop in the natural brewing process.