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中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (6): 667-671.doi: 10.12092/j.issn.1009-2501.2018.06.011

• 临床药理学 • 上一篇    下一篇

奈诺沙星耐药的金黄色葡萄球菌突变体突变位点的研究

李朝霞1,王 睿2,李爱民3,刘又宁3   

  1. 1 火箭军总医院肿瘤科,2 解放军总医院临床药理研究室,3 解放军总医院呼吸科,北京 100088
  • 收稿日期:2018-01-04 修回日期:2018-03-21 出版日期:2018-06-26 发布日期:2018-06-19
  • 通讯作者: 刘又宁,男,博士,主任医师,研究方向:抗生素及细菌耐药机制。 Tel:010-66343466 E-mail:liu-Youning301@vip.sina.com
  • 作者简介:李朝霞,女,博士,副主任医师,研究方向:细菌耐药机制。 Tel:010-66343466 E-mail:18910883463@163.com

Study of the primary target and mutation position in nemonoxacin-resistant mutants of Staphlococcus aureus

LI Zhaoxia1, WANG Rui2,LI Aimin3,LIU Youning3   

  1. 1 Deparment of Oncology,PLA Rocket Force General Hospital,2 Laboratory of Clinical Pharmacology,3 Department of Pneumology,PLA General Hospital,Beijing 100088,China
  • Received:2018-01-04 Revised:2018-03-21 Online:2018-06-26 Published:2018-06-19

摘要:

目的:探讨奈诺沙星对金黄色葡萄球菌的初始作用靶位。了解不同药物浓度筛选出第一步、第二步耐药突变体的突变位点。方法:对不同药物浓度筛选出的耐药突变株进行编码拓扑异构酶Ⅳ C亚单位基因parC(grlA)和促旋酶A、B亚单位基因gyrA和gyrB 喹诺酮耐药决定区的PCR扩增和测序。结果:第一步耐药突变体存在gyrA和gyrB的碱基突变,但均未引起氨基酸的替换。第二步耐药突变体在第一步突变体存在gyrA和gyrB碱基突变的基础上,新发生Ser84→Leu 位点突变。所有奈诺沙星筛选菌株的grlA均未见耐药位点突变。结论:对于金黄色葡萄球菌,DNA促旋酶是奈诺沙星初始作用靶位。Ser84→Leu可能是对奈诺沙星耐药影响最重要的位点。

关键词: 奈诺沙星, 金黄色葡萄球菌, 耐药, 突变位点

Abstract:

AIM: To determine the primary target of nemonoxacin and mutation position in S. aureus by genomic characterization of first and second step mutants. METHODS: Quinolone resistance-determining region(QRDR)mutations of gyrA, gyrB, and grlA of resistant mutants were identified by PCR amplification and gene sequencing. RESULTS: All the 4 first step mutants selected using nemonoxacin contained changes at codon 86, 439, and 440, but did not lead to amino acid substitution. For second-step mutants selected from first-step resistance strains, a novel second gyrA mutation (Ser-84→Leu) mutations was found. No mutations were found in grlA region of QRDR. CONCLUSION: DNA gyrase is the primary target of nemonoxacin in S. aureus. Mutation at position 84 may be the most important factor to influence the sensitivity of S. aureus.

Key words: nemonoxacin, staphlococcus aureus, drug resistance, mutation position

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