Affiliation:
1. Division of Infectious Disease, Children's Hospital and Medical Center, Seattle, Washington.
Abstract
Trimethoprim resistance was investigated in cystic fibrosis isolates of Pseudomonas cepacia. Determination of the MIC of trimethoprim for 111 strains revealed at least two populations of resistant organisms, suggesting the presence of more than one mechanism of resistance. Investigation of the antibiotic target, dihydrofolate reductase, was undertaken in both a susceptible strain and a strain with high-level resistance (MIC, greater than 1,000 micrograms/ml). The enzyme was purified by using ammonium sulfate precipitation, gel filtration, and ion-exchange chromatography. Specific activities, molecular weights, isoelectric points, and substrate kinetics were similar for both enzymes. However, the dihydrofolate reductase from the trimethoprim-resistant strain demonstrated decreased susceptibility to inhibition by trimethoprim and increased susceptibility to inhibition by methotrexate, suggesting that these two enzymes are not identical. We conclude that the mechanism of trimethoprim resistance in this strain with high-level resistance is production of a trimethoprim-resistant dihydrofolate reductase.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
32 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献