耐异烟肼结核分枝杆菌及其katG与inhA基因突变的研究.pdf

.788.中国抗生素杂志2010年10月第35卷第10期

文章编号：1001-8689(2010)10-0788-05

耐异烟肼结核分枝杆菌及其katG与inhA基因突变的研究

陈杨1陈玲1,*张泓2王建华1李娜娜1李开伦1甘辛1张建勇1
(1贵州省遵义医学院附属医院呼吸内科及呼吸医学研究室，遵义563003；2美国Z-BioMed公司，罗克维尔20847)

摘要：目的探讨耐异烟肼临床分离结核分枝杆菌与其katG及inhA基因突变的相关性。方法对87例临床肺结核患者痰标
本进行培养、鉴定及药物敏感性试验，提取菌落DNA、PCR扩增katG和inhA基因片段，并对所有扩增片段进行序列分析。结果
87例菌株经鉴定均为结核分枝杆菌，30(34.5%)例为耐异烟肼菌株，57(65.5%)例异烟肼敏感菌株。30例耐异烟肼株中，18(60%)
株出现katG和(或)inhA基因突变。在突变株中，9(50%)株为katG单基因突变，5(27.8%)株为inhA单基因突变,4(22.2%)株为katG和
inhA双基因联合突变。两个新突变位点(Val230Met和Pro232Gln)为首次发现，已被美国，欧洲和日本的基因库收录。结论该
研究证实结核分枝杆菌katG和inhA基因突变与耐异烟肼相关，为进一步研究异烟肼的抗菌机制奠定了基础。
关键词：耐异烟肼；结核分枝杆菌；聚合酶链式反应；序列分析；基因突变
中图分类号：R378.91+1文献标识码：A

StudyoftherelationshipbetweenresistanttoisoniazidandmutationofKatGand
inhAinMycobacteriumtuberculosisisolates

ChenYang1,ChenLing1,ZhangHong2,WangJian-hua1,LiNa-na1,LiKai-lun1,GanXin1andZhangJian-yong1,
(1DepartmentofRespiratoryMedicine,ZunyiMedicalCollege,Zunyi653003;2Z-BioMedInc,Rockville20847)

AbstractObjectiveTocharacterizerelationshipbetweengenemutationsinkatGandinhAandresistant
clinicalMycobacteriumtuberculosis(M.tb)isolatestoisoniazid.MethodsAtotalof87clinicalMtbisolatesfrom
GuizhouProvincewereusedfordrugsusceptibilitytesting,andmutationanalysisofkatGandinhAgenes.Results
87clinicalisolateswereprovedtobeMtb.30(34.5%)isolateswasresistanttoisoniazid,57(65.5%)isolateswere
sensitivetoisoniazid.Of30isolates,18(60%)isolateshadmutationsinthekatGand(or)inhAgenes.Inthese
mutationisolates,9(50%)mutationsappearedinkatGgene,5(27.8%)ininhA,and4(22.2%)inbothkatGandinhA
genes.TwoofthemutationsinthekatGgene(Val230MetandPro232Gln)werenotreportedpreviouslyandtherefore
weresubmittedtotheGenBankasnewsequences(GQ250582andGQ250583).ConclusionsResultsfromthis
studywithclinicalisolatesfromGuizhouProvincefurtherconfirmedthatmutationsinkatGandinhAgenesarerelated
totheisoniazidresistanceinMtbandtwonewpointmutationsinthekatGgenehavebeenidentifiedfromthestudy,
whichprovideabasisforfurtherunderstandingtheanti-bacteriummechanismofisoniazid.
KeywordsIsoniazidresistance;