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A study on the correlation of quinolone resistance with mutations in DNA gyrase gyrA and topoisomerase IV parC genes in Salmonella typhi

Yonghong Xiao, Wang Qinan

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Abstract

Objective To study the correlation of quinolone resistance with mutations in DNA gyrase gyrA and topoisomerase Ⅳ parC genes in Salmonella typhi. Methods The quinolone resistance determining regions of gyrA and parC in Salmonella typhi 275(a clinically isolated strain, S275) and its spontaneous resistant mutant RG 1 were sequenced. Results The results showed that the sequenced regions of gyrA and parC in S275 had 92.51% and 97.01% homology with those of Escherichia coli respectively, which led to 3 and 6 substitutions in deduced amino acids in gyrA and parC. The gyrA and parC of S275 also had high homology in amino acid sequence as much as 60.92%. In comparison with S275, gyrA of RG 1 had a mutation of T247 G which contributed to the substitution of Ser 83 to Ala in gyrA. No difference was found in parC of S275 and RG 1. The MICs of quinolones on RG 1 were higher than those on S275 by 32 folds or more. Conclusion These results indicated that both DNA gyrase and topoisomerase Ⅳ of S.typhi are targets of quinolones while DNA gyrase is more important as the target molecules. Its mutation seems to be the major mechanism to explain quinolone resistance in S.typhi.

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Objective To study the correlation of quinolone resistance with mutations in DNA gyrase gyrA and topoisomerase Ⅳ parC genes in Salmonella typhi. Methods The quinolone resistance determining regions of gyrA and parC in Salmonella typhi 275(a clinically isolated strain, S275) and its spontaneous resistant mutant RG 1 were sequenced. Results The results showed that the sequenced regions of gyrA and parC in S275 had 92.51% and 97.01% homology with those of Escherichia coli respectively, which led to 3 and 6 substitutions in deduced amino acids in gyrA and parC. The gyrA and parC of S275 also had high homology in amino acid sequence as much as 60.92%. In comparison with S275, gyrA of RG 1 had a mutation of T247 G which contributed to the substitution of Ser 83 to Ala in gyrA. No difference was found in parC of S275 and RG 1. The MICs of quinolones on RG 1 were higher than those on S275 by 32 folds or more. Conclusion These results indicated that both DNA gyrase and topoisomerase Ⅳ of S.typhi are targets of quinolones while DNA gyrase is more important as the target molecules. Its mutation seems to be the major mechanism to explain quinolone resistance in S.typhi.

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Available abstract

Objective To study the correlation of quinolone resistance with mutations in DNA gyrase gyrA and topoisomerase Ⅳ parC genes in Salmonella typhi. Methods The quinolone resistance determining regions of gyrA and parC in Salmonella typhi 275(a clinically isolated strain, S275) and its spontaneous resistant mutant RG 1 were sequenced. Results The results showed that the sequenced regions of gyrA and parC in S275 had 92.51% and 97.01% homology with those of Escherichia coli respectively, which led to 3 and 6 substitutions in deduced amino acids in gyrA and parC. The gyrA and parC of S275 also had high homology in amino acid sequence as much as 60.92%. In comparison with S275, gyrA of RG 1 had a mutation of T247 G which contributed to the substitution of Ser 83 to Ala in gyrA. No difference was found in parC of S275 and RG 1. The MICs of quinolones on RG 1 were higher than those on S275 by 32 folds or more. Conclusion These results indicated that both DNA gyrase and topoisomerase Ⅳ of S.typhi are targets of quinolones while DNA gyrase is more important as the target molecules. Its mutation seems to be the major mechanism to explain quinolone resistance in S.typhi.

Key concepts: DNA gyrase, Quinolone, Topoisomerase IV, Salmonella typhi, Biology, Topoisomerase, Mutant, Microbiology

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