1887

Abstract

Entry of methotrexate (MTX) into the folate prototrophic bacterium was poorly inhibited by folate or its natural derivative folinic acid, suggesting that if MTX is transported via a folate transporter, the affinity of that transporter for MTX is higher than for folate. In the range of concentrations tested, MTX uptake was non-concentrative and decreased in ATP-depleted bacteria. When the external concentration of MTX was increased from 1 × 10 to 1 × 10 , uptake became saturated and was insensitive to ionophores. However when external MTX concentrations were increased to 1 × 10 , uptake increased linearly, and was inhibited by the ionophores carbonyl cyanide -chlorophenylhydrazone (CCCP) and valinomycin, suggesting that the process was energized by the protonmotive force (Δ) at this concentration. A model for MTX entry in . is proposed with respect to these results. The high level of resistance to MTX of the nonsense mutant cannot be entirely explained by a decrease in MTX uptake.

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1985-06-01
2024-11-13
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