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Title: Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium
Authors: Siriporn Kongsoi
Ruchirada Changkwanyeun
Kazumasa Yokoyama
Chie Nakajima
Kanjana Changkaew
Orasa Suthienkul
Yasuhiko Suzuki
Hokkaido University
Kissei Pharmaceutical Co., Ltd.
Thammasat University
Mahidol University
Keywords: Chemistry;Environmental Science
Issue Date: 1-Oct-2016
Citation: Drug Testing and Analysis. Vol.8, No.10 (2016), 1065-1070
Abstract: Copyright © 2015 John Wiley & Sons, Ltd. 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 © 2015 John Wiley & Sons, Ltd.
ISSN: 19427611
Appears in Collections:Scopus 2016-2017

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