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Multiple molecular mechanisms for multidrug resistance transporters

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  • Christopher F. Higgins

    (MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    Present Address: Vice-Chancellor’s Office, Durham University, The University Offices, Old Elvet, Durham DH1 3HP, UK.)

Abstract

Multidrug resistance Most multidrug resistance mechanisms, for agents as diverse as antibiotics, antifungals, antimalarials, herbicides, and also for cancer chemotherapeutics in man, involve a transporter that pumps the drugs out of the cell. The archetypal such transporter, mammalian P-glycoprotein, has been subjected to extensive study for decades but it is only in the past few years that sufficient structural and biochemical data have emerged to give us a mechanistic understanding. Chris Higgins reviews current knowledge on the four major classes of multidrug transporter. Differences and similarities between the four are providing new insights into how multidrug resistance is achieved. This work has not yet solved pressing clinical problems, but may pave the way to strategies to beat or avoid multidrug resistance.

Suggested Citation

  • Christopher F. Higgins, 2007. "Multiple molecular mechanisms for multidrug resistance transporters," Nature, Nature, vol. 446(7137), pages 749-757, April.
    • Handle: RePEc:nat:nature:v:446:y:2007:i:7137:d:10.1038_nature05630
    DOI: 10.1038/nature05630
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    Cited by:

    1. Miquel Serra-Burriel & Matthew Keys & Carlos Campillo-Artero & Antonella Agodi & Martina Barchitta & Achilleas Gikas & Carlos Palos & Guillem López-Casasnovas, 2020. "Impact of multi-drug resistant bacteria on economic and clinical outcomes of healthcare-associated infections in adults: Systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 15(1), pages 1-14, January.
    2. Alexander A. Shcherbakov & Peyton J. Spreacker & Aurelio J. Dregni & Katherine A. Henzler-Wildman & Mei Hong, 2022. "High-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Wellington Francisco Rodrigues & Camila Botelho Miguel & Ana Paula Oliveira Nogueira & Carlos Ueira-Vieira & Tony De Paiva Paulino & Siomar De Castro Soares & Elisabete Aparecida Mantovani Rodrigues D, 2016. "Antibiotic Resistance of Bacteria Involved in Urinary Infections in Brazil: A Cross-Sectional and Retrospective Study," IJERPH, MDPI, vol. 13(9), pages 1-10, September.
    4. Jody L. Andersen & Gui-Xin He & Prathusha Kakarla & Ranjana KC & Sanath Kumar & Wazir Singh Lakra & Mun Mun Mukherjee & Indrika Ranaweera & Ugina Shrestha & Thuy Tran & Manuel F. Varela, 2015. "Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens," IJERPH, MDPI, vol. 12(2), pages 1-61, January.

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