摘要
目的 研究DNA旋转酶、拓扑异构酶Ⅳ在伤寒沙门菌耐喹诺酮类药物的作用。方法对临床分离喹诺酮类敏感伤寒沙门菌 2 75及其自发耐药变异菌RG1 的gyrA、parC基因喹诺酮类耐性决定区进行PCRDNA直接测序分析。结果 表明伤寒沙门菌 2 75gyrA、parC与大肠埃希菌相应DNA序列分别有 92 5 1%与 97 0 1%同源性 ,推定氨基酸序列仅有 3与 6个的差异。伤寒沙门菌gyrA及parC也有较好同源性 ,相应区段氨基酸有 6 0 92 %相同。伤寒沙门菌RG1 与 2 75相比 ,gyrA第 2 47位T→G变异 ,致Ser 83Ala氨基酸替换 ,两者parC完全相同。喹诺酮类药物对RG1 MIC较对伤寒沙门菌2 75上升 32倍或以上。结论 DNA旋转酶、拓扑异构酶Ⅳ为喹诺酮类药物作用靶位 ,但以DNA旋转酶为主 ,该酶变异为伤寒沙门菌耐药的主要原因。
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.
出处
《中华微生物学和免疫学杂志》
CSCD
北大核心
2000年第3期196-198,共3页
Chinese Journal of Microbiology and Immunology
