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Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium
| 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 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/67279 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鈴木 定彦
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