QRDR点突变致解脲脲原体耐巴洛沙星的探讨

The Approach on the Resistance of Ureaplasma Urealyticum to Balofloxacin Incurred by the Spot Mutation of QRDRs

目的研究解脲脲原体(Uu)编码II型拓扑异构酶的基因喹诺酮耐药决定区(QRDR)突变与巴洛沙星耐药的关系。方法对喹诺酮类药物敏感的Uu临床分离株用巴洛沙星进行耐药诱导培养,使之产生第一代和第二代耐药突变株。检测巴洛沙星对Uu标准株、临床分离株、第一代和第二代耐药突变株的最低抑菌浓度(MIC),并对这些菌株的QRDR进行PCR扩增后测序。结果第一代耐药突变株均在编码拓扑异构酶IV基因的QRDR上发生了点突变;第二代耐药突变株则在继承了前代的点突变之后,均在编码DNA促旋酶基因的QRDR上发生了不同的点突变。结论QRDR的点突变可导致Uu对巴洛沙星产生耐药;巴洛沙星对Uu的首要靶酶是拓扑异构酶IV。

Objective To study the correlations between mutations of the quinolone resistance - determining region（QRDR） gene that encodes type Ⅱ topoisomerase of Ureaplasma urealyticum and resistance to Balofloxacin. Methods Clinical isolated strain of Ureaplasma urealyticmn which was sensitive to quinolones was induced by Balofloxacin, then the first and the second generations of resistant mutants were gotten. The MICs of Balofloxacin against Ureaplasma urealyticum reference strain, the clinical isolate as well as the resistant mutants were determined. And QRDRs gene of these Ureaplasma urealyticmn were gotten by PCR, then their sequences were analyzed. Results Each of the first generation of resistant mutants had a spot mutation in the QRDR gene that encodes topoisomerase IV; And the second generation of resistant mutants not only inherited the mutations of their previous gener- ation, but also had an additional mutation in the QRDR gene that encodes DNA gyrase. Conclusion The mutations of QRDRs can resuh in the resistance to Balofloxacin in Ureaplasma urealyticum; The primary target of Balofloxacin in Urcaplasma urealyticmn is topoisomemse Ⅳ.