WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium. Issue 12 (2nd December 2019)

• Record Type: Journal Article
• Authors: Koide, Kentaro; Kongsoi, Siriporn; Nakajima, Chie; Suzuki, Yasuhiko
• Is Part Of: Bioscience, biotechnology, and biochemistry. Volume 83:Issue 12(2019)
• Page Start: 2249
• Page End: 2256
• Publication Date: 2019-12-02
• Subjects: Antimicrobial resistance -- fluoroquinolone -- Salmonella Typhimurium -- IC50; Biotechnology -- Periodicals; Biochemistry -- Periodicals; 660.6
• DOI: 10.1080/09168451.2019.1650634
• Languages: English
• ISSNs: 0916-8451

Abstract

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. Graphical abstract: : WQ-3810 shows high inhibitory activity against quinolone resistant DNA gyrase.