ALQAWI O, POELARENDS G, GEORGES E; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. C1-428.

McGill University, Ste Anne de Bullevue, Quebec, PQ, Canada.

LmrA, a protein in lactocuccus lactis, mediates antibiotic resistance by effluxing different amphiphilic compounds from the cell membrane. It is the first characterized bacterial transporter protein that belongs to the ATP binding cassette (ABC) superfamily and its function is driven by ATP hydrolysis. LmrA is a homolog of P-glycoprotein which is the cause of multidrug resistance of tumor cells during chemotherapy. The expression of LmrA in human lung fibroblast cells conferred the multidrug resistance to these cells similar to the P-glycoprotein. However, the understanding of the molecular interactions and drug recognitions of LmrA is still not clear. In this study, we demonstrated the direct binding of LmrA with the photoactive drug 125 I-AARhodamine 123. This binding was specific and inhibited by increasing concentrations of cold Rhodamine 123. The competition studies showed that Ethedium Bromide, Rhodamine 6G, and Vinblastine highly competed the labeling of LmrA. In addition, the MDR reversing agents such as PSC 833, Cyclosprin A, and Reserpine could inhibit the binding of LmrA with IAA-Rh123.The in gel digestion with V 8 protease of the labeled LmrA revealed a 7 kDa peptide that contains the drug binding domain of the protein. These results showed the similar drug interactions of Lmra with P-glycoprotein indicating the universal molecular mechanisms of drug resistance in infectious diseases and cancer chemotherapy.

Publication Types:

• Meeting Abstracts

Keywords:

• Bacterial Proteins
• Carrier Proteins
• Cell Membrane
• Drug Resistance
• Drug Resistance, Multiple
• Humans
• Membrane Transport Proteins
• Pharmaceutical Preparations
• Rhodamines
• Vinblastine
• rhodamine 6G

Other ID:

• GWAIDS0027070

UI: 102266694

From Meeting Abstracts