Alterations in the DNA topoisomerase IV responsible for quinolone resistance in MRSA and MRSE

DNA 拓扑异构酶 IV 的改变导致 MRSA 和 MRSE 喹诺酮耐药

基本信息

批准号：
08670325
负责人：
NISHINO Takeshi
金额：
$ 0.96万
依托单位：
Kyoto Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670325/
关键词：
DNA gyrase Topoisomerase IV Quinolone MRSA MRSE Resistance Topo IV

项目摘要

We tried to determine partial sequences of the gyrA and parC genes of clinical isolates of Staphylococcus epidermidis and Staphylococcus aureus and attempted to assess the association of mutations in the gyrA and parC genes with fluoroquinolone resistance in MRSA and MRSE Sequence analysis of PCR products from 65 fluoroquinolone-resistant clinical isolates of MRSA was used to examine the quinolone resistance-determining regions of the gyrA gene and the analogous regions of the parC gene. The changes of the serine at position 80 (Ser 80) in parC of 65 strains ested were associated with resistance to quinolone antibacterials. Moreover, sequential acquisition of mutations in parC and gyrA led to higher levels of resistance. These data strongly suggest that ParC mutations as well as GyrA mutations are also important factor for fluoroquinolone resistance in MRSA.Seven fluoroquinolone-resistant mutants of MRSE were examined for mutations in the gyrA and parC genes. While five mutants had a single amino acid changes in ParC,two higher level fluoroquinolone-resistant isolates had a double amino acid change in GyrA (Ser84-Try & Asp94-Gly) and a single amino acid change in ParC.The most important factor for quinolone resistance in S.epidermidis including MRSE seems to be the mutations of target enzymes such as DNA gyrase and DNA topoisomerase IV,and mutations causing decreased drug accumulation due to decreased drug penetration and/or increased drug efflux.

我们试图确定表皮葡萄球菌和金黄色葡萄球菌临床分离株的 gyrA 和 parC 基因的部分序列，并尝试评估 gyrA 和 parC 基因突变与 MRSA 和 MRSE 中氟喹诺酮耐药性的关联。对 65 种氟喹诺酮类药物的 PCR 产物进行序列分析MRSA 耐药临床分离株用于检查 gyrA 基因和类似基因的喹诺酮耐药决定区域parC 基因的区域。所检测的65株菌株的parC中80位丝氨酸（Ser 80）的变化与喹诺酮类抗菌药物的耐药性相关。此外，parC 和 gyrA 突变的连续获得导致更高水平的耐药性。这些数据强烈表明，ParC 突变和 GyrA 突变也是 MRSA 氟喹诺酮耐药的重要因素。对 MRSE 的 7 个氟喹诺酮耐药突变体进行了 gyrA 和 parC 基因突变的检查。虽然五个突变体在 ParC 中具有单个氨基酸变化，但两个较高水平的氟喹诺酮抗性分离株在 GyrA 中具有双氨基酸变化（Ser84-Try 和 Asp94-Gly），并且在 ParC 中具有单个氨基酸变化。表皮葡萄球菌中包括MRSE在内的喹诺酮类药物耐药似乎是由于DNA旋转酶和DNA拓扑异构酶IV等靶酶的突变引起的，并且由于突变导致药物蓄积减少。药物渗透和/或增加的药物流出。