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R-factor-mediated resistance to sulfonamides by a plasmid-borne, drug-resistant dihydropteroate synthase
Abstract:
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.
Insights
A newly discovered plasmid-borne enzyme variant of dihydropteroate synthase confers sulfonamide resistance in bacteria. This episomal enzyme
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Folic acid biosynthesis is essential for bacterial growth.
- Sulfonamides are antibiotics that inhibit dihydropropteroate synthase, a key enzyme in folic acid synthesis.
- R-factors (resistance plasmids) can mediate antibiotic resistance in bacteria.
Purpose of the Study:
- To investigate the mechanism of R-factor-mediated sulfonamide resistance.
- To identify a potential episome-specified variant of dihydropteroate synthase.
Main Methods:
- Complementation of temperature-sensitive bacterial mutants.
- Enzyme activity assays in bacterial extracts.
- Plasmid transfer experiments.
Main Results:
- An R-factor (R1dr19) rescued temperature-sensitive bacterial mutants with defects in chromosomal dihydropteroate synthase.
- Bacteria harboring R1dr19 exhibited dihydropteroate synthase activity less susceptible to sulfonamide inhibition.
- The R-factor, along with sulfonamide resistance, was transferable between bacteria.
Conclusions:
- An episome-specified variant of dihydropteroate synthase contributes to sulfonamide resistance.
- Diploidy for the target enzyme, due to the presence of a plasmid-borne variant, is a proposed mechanism for R-factor-mediated sulfonamide resistance.