Kopytek S J, Dyer J C, Knapp G S, Hu J C
Department of Biochemistry and Biophysics and Center for Advanced Biomolecular Research, Texas A&M University, College Station, Texas 77843-2128, USA.
Antimicrob Agents Chemother. 2000 Nov;44(11):3210-2. doi: 10.1128/AAC.44.11.3210-3212.2000.
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.
许多大肠杆菌实验室菌株对甲氨蝶呤(MTX)具有抗性,甲氨蝶呤是一种结合二氢叶酸还原酶(DHFR)的叶酸类似物。使tolC或acrA失活的突变会导致对MTX敏感。此外,具有DHFR活性的融合蛋白的过表达通过滴定细胞内MTX来逆转这种敏感性。这些结果表明,MTX在acrA或tolC发生突变使依赖于TolC的AcrAB多药耐药性外排泵失活的细胞中积累。