张一沙 吴颖 范兴丽 蒋锦琴 孙爱华

[摘要] 目的 研究解脲脲原体喹诺酮类药物耐药机制。 方法 用支原体培养、鉴定和药敏试剂盒分离获得77株解脲脲原体并检测对3种喹诺酮类药物的耐药性，同时PCR法扩增临床分离株的gyrA和parC基因喹诺酮耐药决定区并进行测序分析。 结果 对3种喹诺酮均敏感3株，74株至少对1种药物呈现不同程度耐药。gyrA和parC基因喹诺酮耐药决定区测序发现上述敏感株和2株耐药株不发生突变，其余72株耐药株gyrA和parC发生D112E和/或S83L突变。 结论 解脲脲原体gyrA和parC基因喹诺酮耐药决定区突变与耐药密切相关。

[关键词] 解脲脲原体；gyrA、parC基因；突变；序列分析；耐药性

[中图分类号] R446.5[文献标识码] A[文章编号] 1673-9701（2012）16-0001-03

To study of resistance mechanisms of Ureaplasma urealyticum to quinolones

ZHANG Yisha1 WU Ying2 FAN Xingli3 JIANG Jinqin3 SUN Aihua3

1.Department of Urological Surgery, Taizhou Integrative Medicine Hospital in Zhejiang Province, Wenling 317523, China; 2.Department of Clinical Laboratory, Taizhou Integrative Medicine Hospital in Zhejiang Province, Wenling 317523, China; 3.Department of Basic Medicine, Zhejiang Medical College, Hangzhou 310053, China

[Abstract] Objective To study the resistance mechanisms of Ureaplasma urealyticum to quinolones. Methods Mycoplasma detection kits were used to culture and identify mycoplasma as well as drug sensitivity. PCR and DNA sequencing were conducted to analyze QRDR associated genes of gyrA and parC in 77 isolates. Results There were only 3 isolates susceptible to all quinolones, and 74 isolates showed varying degree resistance to at least one kind of quinolone. Sequencing analysis of gyrA and parC revealed that 3 susceptible isolates and 2 resistant isolates had no mutation, 72 resistant isolates had mutation of D112E and/or S83L in gyrA and parC. Conclusion Mutations in gyrA and parC genes play an important role in the development of quinolones resistance in Ureaplasma urealyticum.

[Key words] Ureaplasma urealyticum; GyrA and parC genes; Mutation; Sequence analysis; Drug resistance

慢性前列腺炎是男性最常见的泌尿生殖道疾病之一，解脲脲原体（Ureaplasma urealyticum，Uu）是引起非细菌性慢性前列腺炎的主要病原体[1]。喹诺酮类药物是一类人工合成的具有高效广谱抗菌作用的药物。随着喹诺酮类药物的大量和广泛的应用，解脲脲原体临床分离株对该类药物的敏感性逐渐下降并出现耐药[2-5]。

国内外对解脲脲原体对喹诺酮类药物的耐药机制研究不多，喹诺酮类药物的作用靶酶为Ⅱ型拓扑异构酶（包括DNA螺旋酶和拓扑异构酶Ⅳ），喹诺酮类药物耐药是由于编码靶酶的基因突变导致靶酶的氨基酸序列改变，gyrA和parC基因分别编码DNA螺旋酶和拓扑异构酶Ⅳ，GyrA和ParC氨基酸发生替换突变抑制细菌DNA螺旋酶和拓扑异构酶Ⅳ的活性导致耐药[6]。本研究从慢性前列腺炎患者前列腺液……