PMID:11036056
| Citation |
Kopytek, SJ, Dyer, JC, Knapp, GS and Hu, JC (2000) Resistance to methotrexate due to AcrAB-dependent export from Escherichia coli. Antimicrob. Agents Chemother. 44:3210-2 |
|---|---|
| Abstract |
Many laboratory strains of Escherichia coli are resistant to methotrexate (MTX), a folate analogue that binds dihydrofolate reductase (DHFR). Mutations that inactivate either tolC or acrA confer MTX sensitivity. Further, overexpression of a fusion protein with DHFR activity reverses this sensitivity by titrating out intracellular MTX. These results suggest that MTX accumulates in cells where mutations in acrA or tolC have inactivated the TolC-dependent AcrAB multidrug resistance efflux pump. |
| Links | |
| Keywords |
Bacterial Outer Membrane Proteins/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Biological Transport; Drug Resistance, Microbial/physiology; Enzyme Inhibitors/pharmacology; Escherichia coli/drug effects; Escherichia coli/enzymology; Escherichia coli/metabolism; Escherichia coli Proteins; Folic Acid Antagonists/pharmacology; Lipoproteins/genetics; Lipoproteins/metabolism; Membrane Transport Proteins; Methotrexate/pharmacology; Mutation; P-Glycoprotein/genetics; P-Glycoprotein/metabolism; Tetrahydrofolate Dehydrogenase/metabolism |
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