喹诺酮类药物诱导人型支原体耐药机理研究

The resistance of mycoplasma hominis induced by antibiotic subinhibitory concentration of quinolones

目的 探讨人型支原体 (Mh)对喹诺酮类药物的耐药机理 ,指导合理使用抗生素。方法以含氧氟沙星、左旋氧氟沙星、盐酸环丙沙星的培养基培养标准敏感株及临床敏感株Mh12代后 ,将其gyrA基因、parE基因扩增 ,分析其核苷酸序列。结果 3种药物诱导株均产生耐药及交叉耐药性 ,氧氟沙星、左旋氧氟沙星诱导Mh发生 70位G→A的突变 ,导致 42 6位的天冬氨酸转变为天冬酰胺 ;盐酸环丙沙星诱导Mh发生 113位C→T的突变 ,导致 83位的丝氨酸转变为亮氨酸。结论 Mh长期接触低浓度喹诺酮类药物会产生耐药性 ,gyrA、parE基因中的点突变可能是耐药机制的一部分。

Objective To study the resistance of Mycoplasma hominis (Mh) to quinolones, and to instruct reasonable application of antibiotics clinically.Methods The gyrA genes and the parE genes of a standard strain Mh induced by ofloxacin (OFX), levofloxacin (LFX), ciprofloxacin (CFX) respectively were amplified by polymerase chain reaction (PCR), and the nucleotide sequences were compared to a susceptible strain Mh by DNA sequencing.Results All induced Mh showed resistance and cross resistance to quinolones. CFX induced Mh had nucleotide 113 C→T mutation which leads to substitution of Ser 83 by Leu in the GyrA protein; OFX induced Mh and LFX induced Mh had nucleotide 70 G→A mutation which leads to substitution of Asp 426 by Asn in the ParE protein.Conclusion The strains of Mh can produce resistance and cross resistance characteristics when they contact with antibiotic subinhibitory concentration of quinolones. The change is associated with mutants of gyrA genes and parE genes.