A bacterial antibiotic-resistance gene that complements the human multidrug-resistance P-glycoprotein gene

摘要: Bacteria have developed many fascinating antibiotic-resistance mechanisms. A protein in Lactococcus lactis, LmrA, mediates antibiotic resistance by extruding amphiphilic compounds from the inner leaflet of cytoplasmic membrane. Unlike other known bacterial multidrug-resistance proteins, LmrA is an ATP-binding cassette (ABC) transporter. The human P-glycoprotein, encoded MDR1 gene, also ABC transporter, overexpression which one principal causes cancers to chemotherapy. We expressed lmrA lung fibroblast cells. Surprisingly, was targeted plasma membrane and conferred typical multidrug on these pharmacological characteristics P-glycoprotein-expressing fibroblasts were very similar, affinities both proteins for vinblastine magnesium-ATP indistinguishable. Blockers P-glycoprotein-mediated inhibited LmrA-dependent drug resistance. Kinetic analysis dissociation membranes insect cells revealed presence two allosterically linked drug-binding sites indistinguishable those P-glycoprotein. These findings implications reversal pathogenic microorganisms. Taken together, they demonstrate that P-glycoprotein are functionally interchangeable this type efflux pump conserved bacteria man.