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Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones
- Source :
- Journal of Infection and Chemotherapy. 21(8):604-609
- Publication Year :
- 2015
- Publisher :
- Elsevier, 2015.
-
Abstract
- Quinolones have long been used as the first-line treatment for Campylobacter infections. However, an increased resistance to quinolones has raised public health concerns. The development of new quinolone-based antibiotics with high activity is critical for effective, as DNA gyrase, the target of quinolones, is an essential enzyme for bacterial growth in several mechanisms. The evaluation of antibiotic activity against Campylobacter jejuni largely relies on drug susceptibility tests, which require at least 2 days to produce results. Thus, an in vitro method for studying the activity of quinolones against the C. jejuni DNA gyrase is preferred. To identify potent quinolones, we investigated the interaction of C. jejuni DNA gyrase with a number of quinolones using recombinant subunits. The combination of purified subunits exhibited DNA supercoiling activity in an ATP dependent manner. Drug concentrations that inhibit DNA supercoiling by 50% (IC50s) of 10 different quinolones were estimated to range from 0.4 (sitafloxacin) to >100 µg/mL (nalidixic acid). Sitafloxacin showed the highest inhibitory activity, and the analysis of the quinolone structure-activity relationship demonstrated that a fluorine atom at R-6 might play the important role in the inhibitory activity against C. jejuni gyrase. Measured quinolone IC50s correlated well with minimum inhibitory concentrations (R = 0.9943). These suggest that the in vitro supercoiling inhibition assay on purified recombinant C. jejuni DNA gyrase is a useful and predictive technique to monitor the antibacterial potency of quinolones. And furthermore, these data suggested that sitafloxacin might be a good candidate for clinical trials on campylobacteriosis.
- Subjects :
- DNA, Bacterial
Microbiology (medical)
Sitafloxacin
Nalidixic acid
medicine.drug_class
Molecular Conformation
Microbial Sensitivity Tests
Quinolones
Campylobacter jejuni
DNA gyrase
DNA supercoiling activity
Microbiology
law.invention
Inhibitory Concentration 50
Structure-Activity Relationship
law
medicine
Topoisomerase II Inhibitors
Pharmacology (medical)
biology
biology.organism_classification
Quinolone
Recombinant Proteins
Anti-Bacterial Agents
Infectious Diseases
Biochemistry
DNA Gyrase
Recombinant DNA
DNA supercoil
Fluoroquinolones
medicine.drug
Subjects
Details
- Language :
- English
- Volume :
- 21
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of Infection and Chemotherapy
- Accession number :
- edsair.doi.dedup.....ec25cc17db3ec5f1825a9ea362d3a00e