WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium-Reference-Cited by-同舟云学术

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

Published:2019-12-02 Issue:12 Volume:83 Page:2249-2256
ISSN:0916-8451
Container-title:Bioscience, Biotechnology, and Biochemistry
language:en
Short-container-title:

Author:

Koide Kentaro¹,Kongsoi Siriporn²,Nakajima Chie¹³,Suzuki Yasuhiko¹³

Affiliation:

1. Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan

2. Department of Veterinary Public Health, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand

3. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan

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.

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

Link

http://academic.oup.com/bbb/article-pdf/83/12/2249/36828069/bbb2249.pdf

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