The structure and function of drug pumps.
Resistance to drugs has emerged in biological systems as diverse as cancer cells undergoing chemotherapy and microbial pathogens undergoing treatment with antimicrobials. This medical problem is escalating and there is an urgent need for the development of new classes of drugs. In the case of pathogenic bacteria, we are rapidly approaching a scenario where there will be no effective antibiotics in the armoury of drugs available for treating the infectious diseases that these bacteria cause, returning us to the pre-antibiotic era when infectious diseases were rife because they were untreatable. One of the most frequently employed resistance strategies in both prokaryotes and eukaryotes is the transmembrane-protein-catalysed extrusion of drugs from the cell, with these proteins acting like bilge pumps, reducing the intracellular drug concentration to subtoxic levels. There is currently much scientific interest in understanding how these pumps operate, so that we might design transport inhibitors that would block them, allowing a renaissance for drugs that are no longer effective owing to their efflux.
Borges-Walmsley
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Division of Infection and Immunity, Institute of Biomedical & Life Sciences, Robertson Building, University of Glasgow, G11 6NU, Glasgow, UK. a.walmsley@bio.gla.ac.uk
Walmsley
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D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000502:physiology*; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D002352:Carrier Proteins