Mechanism of Sulfonamide Resistance and Synergism in Pathogens.
Abstract
It is the primary objective of our proposed research to explore the mechanism of sulfonamide resistance and synergism at the molecular level. Our experimental results both from cell-free and whole cell bacterial studies with naturally occurring clinical isolates of N. meningitidis and N. gonorrhoeae revealed that drug resistance to sulfonamide was achieved through an alteration in dihydropteroate synthetase structure expressed as a reducing binding capacity for the inhibitor, sulfonamide, rather than a change in affinity for the substrate, paraaminobenzoate (pABA). The enzyme dihydropteroate synthetases from Neisseria meningococci were found to possess much better chromatographic behaviors toward gel-filtrations as well as ion-exchangers. The results of MIC studies indicated that many strains of N. gonorrhoeae exhibiting sulfonamide resistance are found to be also relatively insensitive to trimethropim. The dihydrofolate reductase of a sulfonamide sensitive strain (CDC-9) is further purified to a homogeneous state by a methotrexate affinity chromatography. A molecular weight of 20,300 is estimated for the gonococcal reductase by analytical gel-filtration. Enzymes of dihydrofolate reductases from resistant strains (they are also trimethoprim resistant) behave nicely toward purification procedures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1978
- Accession Number
- ADA060461
Entities
People
- Leonard Corman
- Richard I. Ho