淋球菌gyrA和parC基因突变与氟喹诺酮类药物关系的研究  

Correlation between Fluoroquinolone Resistance and Mutations of Neisseria gonorrhoeae gyrA and parCgenes

作　　者：邹明祥[1] 夏忠弟[2] 陈淑贞[2] 唐银[1] 刘海连[1] 张国强 

机构地区：[1]中南大学湘雅医院检验科,长沙410008 [2]中南大学湘雅医学院微生物教研室 [3]湖南省性病防治研究所

出　　处：《中华皮肤科杂志》2002年第3期199-202,共4页Chinese Journal of Dermatology

摘　　要：目的探讨淋球菌gyrA和parC基因突变与淋球菌耐氟喹诺酮类药物之间的关系。方法①纸片扩散法检测58株淋球菌对5种氟喹诺酮类药物的敏感性。②E测定法定量检测环丙沙星的最小抑菌浓度(MIC)。③PCR技术扩增gyrA和parC基因的喹诺酮耐药决定区(QRDR)相关序列并作测序分析。结果①对环丙沙星、氧氟沙星、氟罗沙星、洛美沙星、依诺沙星同为敏感、中介、耐药者分别为2株、4株和39株。②环丙沙星MIC为敏感、中介、耐药分别为2株、17株和39株。③环丙沙星MIC为0.004～0.016μg/mL的2株淋球菌gyrA和parC基因均未发生突变;MIC为0.064～0.094μg/mL的菌株仅发生gyrA单位点突变;而MIC≥0.25μg/mL的菌株均发生gyrA双位点突变。MIC≤0.25μg/mL的菌株无parC基因突变,而MIC≥1.0μg/mL的菌株除出现gyrA双位点突变外均同时发生parC单位点突变。④在发生突变的16株菌中,Ser91(TCC)→Phe(TTC)突变为15株。结论①gyrA基因突变介导淋球菌对氟喹诺酮类药物低和中水平耐药,而对氟喹诺酮类药物高水平耐药需要parC基因突变的共同参与。②gyrA基因Ser91→Phe的突变是导致淋球菌对氟喹诺酮类药物耐药的关键突变。ObjectiveToevaluatethecorrelationbetweenfluoroquinoloneresistanceinNeisseriagonor-rhoeaeandmutationsingyrAandparCgenes.Methods①Thesusceptibilities58clinicalisolatesofN.gonorrhoeaeto5fluoroquinolonesweretestedbydiscdiffusionmethod.②Theminimuminhibitoryconcentration(MIC)ofciprofloxacinwasdeterminedbyE-test.③Thefragmentsincludingthequinoloneresistance-determiningregion(QRDR)wereamplifiedbyPCRingyrAgeneof18strains,andparCgeneof8strains,andtheirrelativefragmentsweredirectlysequenced.Results①Thenumbersofstrainssimultaneouslysensitive,intermediateandresistanttociprofloxacin,ofloxacin,lomefloxacin,fleroxacinandenoxacinwere2,4and39,respectively.②TherangeofciprofloxacinMICwas0.004～12.0μg/mLin58strains.Thenumbersofstrainssensitive,intermediateandresistanttociprofloracinwere2,17and39,respectively.③ThestrainswithciprofloxacinMICfrom0.004～0.016μg/mLhadnomutationingyrAandparCgenes.ThestrainswithMICfrom0.064to0.094μg/mLcarriedasinglepointmutationingyrAgene,whilethestrainswithMIC≥0.25μg/mLcontainedtwomutationsingyrAgene.Inaddition,thestrainswithMIC≤0.25μg/mLhadnomutationinparCgeneandthestrainswithMIC≥1.0μg/mLexhibitedasinglepointmutationinparCgeneandtwomutationsingyrAgene.④Of16strainscontainingmutationingyrAgene,15strainsexhibitedsubstitutionofSer91(TCC)→Phe(TTC).Conclusions①MutationswithingyrAgenemediatelowandmoderatelevelsfluoroquinoloneresistancewhilemutationswithinparCgeneparticipateinhighlevelfluoro-quinoloneresistanceinN.gonorrhoeae.②SubstitutionofSer91→PheingyrAgeneisthepivotalmutationresultinginfluoroquinoloneresistanceinN.gonorrhoeae.

关 键 词：淋病奈瑟氏球菌 微生物敏感性试验 抗感染药 氟喹诺酮 点突变 

分 类 号：R446.5[医药卫生—诊断学]