Evidence for a Cryptic Gene that Enables E. Coli to Specifically Transport Folate Analogs
The effectiveness of the sulfonamide antibiotics has been attributed to the inability of most bacteria to utilize environmental folate. Escherichia coli and other bacteria depend on de novo synthesis of folate. We have previously isolated pabA- mutants that can grow on p-aminobenzoyl glutamate, a breakdown product of folic acid (Hussein, Green, and Nichols, J. Bact. 1998, 180, 6260–6268). Growth correlated with overproduction of AbgT, an apparent transporter located at the end of a sequence resembling an operon. Using measurements of minimal inhibitory concentration (MIC) for a variety of drugs, we show that over-expression of abgT in wild-type cells imparts a large increase in sensitivities to aminopterin and methotrexate. Inhibition seems to be specific for folate analogs, as there was little difference in the MIC values for other drugs, including trimethoprim, tetracycline, nalidixic acid, kanamycin, rifampicin, chloramphenicol, salicylic acid, and streptomycin. The abg locus may be cryptic for transport of folate analogs or end products of folate catabolism.
KeywordsHydrolysis Methotrexate Folate Pseudomonas Streptomycin
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