Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium

Kongsoi, Siriporn; Changkwanyeun, Ruchirada; Yokoyama, Kazumasa et al.

Drug Testing and Analysis, 2016, 8(10), 1065-1070

Permalink : https://hdl.handle.net/2115/67279

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論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/67279
タイトル
Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium
著者
Kongsoi, Siriporn ; Changkwanyeun, Ruchirada ; Yokoyama, Kazumasa ; Nakajima, Chie ; Changkaew, Kanjana ; Suthienkul, Orasa ; Suzuki, Yasuhiko
著者名
Kongsoi, Siriporn
著者名
Changkwanyeun, Ruchirada
著者名
Yokoyama, Kazumasa
e-Rad_Researcher
60435964
著者名
Nakajima, Chie
著者名
Changkaew, Kanjana
著者名
Suthienkul, Orasa
e-Rad_Researcher
90206540
著者名
Suzuki, Yasuhiko
言語
英語
キーワード
Salmonella Typhimurium
amino acid substitutions
quinolone resistance
発行日
2016-10
出版者
Wiley-Blackwell
収録物名
Drug Testing and Analysis
巻(号)
8(10)
ページ
1065-1070
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
権利情報
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 http://dx.doi.org/10.1002/dta.1910. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
PISSN
1942-7603
EISSN
1942-7611
NCID
AA12629829
関連情報
PMID
26514939
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1002/dta.1910