R-Factor-Mediated Resistance to Sulfonamides by a Plasmid-Borne, Drug-Resistant Dihydropteroate Synthase

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RESUMO

Evidence was found for the existence of an episome-specified variant of the enzyme dihydropteroate synthase involved in folic acid formation. Since the plasmid-borne enzyme showed a decreased susceptibility for sulfonamide inhibition and was transferable together with resistance to this drug, it is proposed that diploidy for the target enzyme in some cases could be the mechanism of R-factor-mediated resistance to sulfonamides. Two types of evidence were obtained. One was the rescue from temperature sensitivity of bacterial mutants with a lesion in the chromosomal dihydropteroate synthase by the R factor R1dr19 mediating sulfonamide resistance. The other evidence was found by the determination of dihydropteroate forming activity in extracts from R− and R+ bacteria. Cells harboring R1dr19 were found to contain an enzyme activity which was far less susceptible to sulfonamide inhibition than the corresponding activity from R− cells.

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