淋病奈瑟菌的耐药性与喹诺酮耐药基因突变的相关性分析  

Correlation of mutation patterns in gyrA gene in Neisseria gonorrhoeae isolates with quinolone resistance

作　　者：张怡 吴颖[2] 孙爱华[3] 

机构地区：[1]浙江省温岭市中医院,温岭317500 [2]浙江省台州市中西医结合医院,台州317523 [3]浙江医学高等专科学校,杭州310053

出　　处：《海峡药学》2011年第10期215-218,共4页Strait Pharmaceutical Journal

摘　　要：目的分析本地区淋病奈瑟菌临床菌株gyrA基因突变与喹诺酮类药物耐药的相关性。方法采用琼脂稀释法检测37株淋病奈瑟菌临床菌株对6种抗生素的最小抑菌浓度(MIC),PCR法扩增淋病奈瑟菌临床菌株gyrA基因片段并测序。结果 37株淋病奈瑟菌临床菌株对大观霉素、头孢曲松、四环素、青霉素、氧氟沙星和环丙沙星的耐药率分别为0、0、70.3%、75.7%、91.9%和97.3%。有1株淋病奈瑟菌临床菌株对环丙沙星敏感,其MIC为0.03μg.mL-1。检测36株对环丙沙星耐药淋病奈瑟菌临床菌株的gyrA基因,发现7种编码氨基酸的核苷酸序列突变,其中最常见的突变是gyrA基因编码的91位丝氨酸突变为苯丙氨酸(32/26)和95位天冬氨酸突变为甘氨酸(14/36)。所有耐药淋病奈瑟菌临床菌株S91都发生突变,包括S91F、S91Y和S91C三种突变。31株gyrA基因编码95位天冬氨酸也可发生三种突变,D95A、D95G和D95N突变分别有7、14和10株。92位丙氨酸的核苷酸突变发生概率低为11.1%(4/36),其中2株伴有D95A或D95N。结论青霉素、四环素、氧氟沙星和环丙沙星已不能作为治疗淋病的常规用药,大观霉素和头孢曲松仍可作为本地区治疗淋病的一线药物。gyrA基因突变在淋病奈瑟菌对喹诺酮类药物耐药中起重要作用。OBJECTIVE To analyze the correlation between mutation in gyrA gene and quinolone resistance in Neisseria gonorrhoeae isolates in the local area. METHODS The MICs of 6 antimicrobials were determined by agar dilution method. PCR and DNA sequencing were conducted to analyze gene of gyrA in 37 isolates. RESULTS The resistance rate of the 37 isolates were 0, 0, 70.3 %, 75.7 %, 91.9 % and 97.3 % to spectinomycin, cefriaxone, tetracycline, penicillin, ofloxaein and eiprofloxacin respectively. Results of sequencing analysis of gyrA gene, no mutation in gyrA gene were detected in one ciprofloxacin-sensitive isolate and for which the MIC was 0.03μg. mL- 1. Of the 36 ciprofloxacin-resistanee isolates, there were 7 type of mutations in gyrA gene, the most common mutations were serine to phenylaIanine at position 91 （in 32 of 36 strains） and aspartic acid to glycine at position 95 （in 14 of 36 strains） in gyrA.Alterations at S91 in gyrA were detected in all ciprofloxacin-resistance isolates, included S91F, S91Y and S91C.31 ciprofloxaein-resistance isolates carried three type mutations at D95 in gyrA gene, included D95G, D95A and D95N. Four eiprofloxacin-resistance isolates carried A92P mutation, and two accompanied by D95A or D95N mutation. Conclusions Tetracycline, penicillin, ofloxacin and ciprofloxacin should not be routine therapy for gonorrhoea, speetinomyein and cefriaxone is recommended in the treatment of N.gonorrhoeae infections in the local area. Mutations in gyrA gene play an important role in the development of quinolone resistance in N. gonorrhoeae.

关 键 词：淋病奈瑟菌 GYRA基因 突变 序列分析 耐药性 

分 类 号：R978.1[医药卫生—药品]