Identification of a novel plasmid-encoded dihydrofolate reductase mediating high-level resistance to trimethoprim.

A Proteus mirabilis strain, isolated in South Africa, carried a 79kb transferable plasmid (pUK672) which encoded high-level resistance to trimethoprim (minimum inhibitory concentration greater than 2048 mg/l). The trimethoprim resistance was mediated by a dihydrofolate reductase which had completely different properties from any plasmid-encoded dihydrofolate reductase previously described. This enzyme has been designated type VI. The type VI enzyme is small (10,000 daltons) and is unstable in vitro. It is highly resistant to inhibition by both trimethoprim and methotrexate.