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Resistance to methotrexate due to AcrAB-dependent export from Escherichia coli
S J Kopytek1, J C Dyer, G S Knapp
1Department of Biochemistry and Biophysics and Center for Advanced Biomolecular Research, Texas A&M University, College Station, Texas 77843-2128, USA.
Antimicrobial Agents and Chemotherapy
|October 19, 2000
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.