Plasmid-mediated trimethoprim-resistance in Staphylococcus aureus. Characterization of the first gram-positive plasmid dihydrofolate reductase (type S1)
- PMID: 3606580
- PMCID: PMC1147852
- DOI: 10.1042/bj2430309
Plasmid-mediated trimethoprim-resistance in Staphylococcus aureus. Characterization of the first gram-positive plasmid dihydrofolate reductase (type S1)
Abstract
The trimethoprim-resistance gene located on plasmid pSK1, originally identified in a multi-resistant Staphylococcus aureus from Australia, encodes the production of a dihydrofolate reductase (type S1), which confers a high degree of resistance to its host and is quite unlike any plasmid-encoded dihydrofolate reductase hitherto described. It has a low Mr (19,700) and has a higher specific activity than the constitutive Gram-negative plasmid dihydrofolate reductases. The type S1 enzyme is heat-stable and has a relatively low affinity for the substrate, dihydrofolate (Km 10.8 microM). It is moderately resistant to trimethoprim, and is competitively inhibited by this drug with an inhibitor-binding constant of 11.6 microM. This is the first identification and characterization of a plasmid-encoded trimethoprim-resistant dihydrofolate reductase derived from a Gram-positive species.
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