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Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium

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Title: Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium
Authors: Kongsoi, Siriporn Browse this author
Changkwanyeun, Ruchirada Browse this author
Yokoyama, Kazumasa Browse this author
Nakajima, Chie Browse this author →KAKEN DB
Changkaew, Kanjana Browse this author
Suthienkul, Orasa Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: Salmonella Typhimurium
amino acid substitutions
quinolone resistance
Issue Date: Oct-2016
Publisher: Wiley-Blackwell
Journal Title: Drug Testing and Analysis
Volume: 8
Issue: 10
Start Page: 1065
End Page: 1070
Publisher DOI: 10.1002/dta.1910
PMID: 26514939
Abstract: The prevalence of quinolone-resistant Salmonella has become a public health concern. Amino acid substitutions have generally been found within the quinolone resistance-determining region in subunit A of DNA gyrase (GyrA) of Salmonella Typhimurium. However, direct evidence of the contribution of these substitutions to quinolone resistance remains to be shown. To investigate the significance of amino acid substitutions in S. Typhimurium GyrA to quinolone resistance, we expressed recombinant wild-type (WT) and five mutant DNA gyrases in Escherichia coli and characterized them in vitro. WT and mutant DNA gyrases were reconstituted in vitro by mixing recombinant subunits A and B of DNA gyrase. The correlation between the amino acid substitutions and resistance to quinolones ciprofloxacin, levofloxacin, nalidixic acid, and sitafloxacin was assessed by quinolone-inhibited supercoiling assays. All mutant DNA gyrases showed reduced susceptibility to all quinolones when compared with WT DNA gyrases. DNA gyrase with a double amino acid substitution in GyrA, serine to phenylalanine at codon 83 and aspartic acid to asparagine at 87 (GyrA-S83F-D87N), exhibited the lowest quinolone susceptibility amongst all mutant DNA gyrases. The effectiveness of sitafloxacin was shown by the low inhibitory concentration required for mutant DNA gyrases, including the DNA gyrase with GyrA-S83F-D87N. We suggest sitafloxacin as a candidate drug for the treatment of salmonellosis caused by ciprofloxacin-resistant S. Typhimurium. Copyright (C) 2015 John Wiley & Sons, Ltd.
Rights: This is the peer reviewed version of the following article: S. Kongsoi, R. Changkwanyeun, K. Yokoyama, C. Nakajima, K. Changkaew, O. Suthienkul, Y. Suzuki. Amino Acid Substitutions in GyrA Affect Quinolone Susceptibility in Salmonella Typhimurium. Drug Test. Anal. 2016, 8, 1065, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: article (author version)
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 定彦

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