WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium.

Abstract

The inhibitory effect of WQ-3810 on DNA gyrase was assayed to evaluate the potential of WQ-3810 as a candidate drug for the treatment of quinolone resistant Salmonella Typhymurium infection. The inhibitory effect of WQ-3810, ciprofloxacin and nalidixic acid was compared by accessing the drug concentration that halves the enzyme activity (IC50) of purified S. Typhimurium wildtype and mutant DNA gyrase with amino acid substitution at position 83 or/and 87 in subunit A (GyrA) causing quinolone resistance. As a result, WQ-3810 reduced the enzyme activity of both wildtype and mutant DNA gyrase at a lower concentration than ciprofloxacin and nalidixic acid. Remarkably, WQ-3810 showed a higher inhibitory effect on DNA gyrase with amino acid substitutions at position 87 than with that at position 83 in GyrA. This study revealed that WQ-3810 could be an effective therapeutic agent, especially against quinolone resistant Salmonella enterica having amino acid substitution at position 87.

• Authors: Kentaro Koide, Siriporn Kongsoi, Chie Nakajima, Yasuhiko Suzuki
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 83 Issue 12 Pg. 2249-2256 (Dec 2019) ISSN: 1347-6947 [Electronic] England
• PMID: 31382821 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Azetidines
• Enzyme Inhibitors
• Fluoroquinolones
• Quinolones
• Recombinant Proteins
• WQ-3810
• DNA Gyrase

Topics

• Anti-Bacterial Agents (pharmacology)
• Azetidines (pharmacology)
• DNA Gyrase (drug effects, genetics, metabolism)
• Drug Resistance, Bacterial
• Enzyme Inhibitors (pharmacology)
• Fluoroquinolones (pharmacology)
• Inhibitory Concentration 50
• Microbial Sensitivity Tests
• Quinolones (pharmacology)
• Recombinant Proteins (drug effects, metabolism)
• Salmonella typhimurium (drug effects, enzymology)