结核分枝杆菌embB基因306位点突变与乙胺丁醇药敏表型及耐多药关系的研究  

Association between embB mutation at codon 306 and drug resistance and MDR in Mycobacterium tuberculosis for ethambutol

作　　者：刘厚明[1] 肖颜玉[1] 李天品 罗凯[1] 叶飞娣[1] 韩红星[1] 邓群益[2] 陈心春[3] 单万水[1] 

机构地区：[1]深圳市第三人民医院检验科,广东深圳518112 [2]深圳市第三人民医院肺病一区,广东深圳518112 [3]深圳市第三人民医院肝病研究所,广东深圳518112

出　　处：《热带医学杂志》2015年第6期731-734,共4页Journal of Tropical Medicine

基　　金：深圳市科技创新委员会基金(JCYJ2013040116479996;JCYJ20140411113637598);深圳市结核病临床重点专科专项基金

摘　　要：目的探讨结核分枝杆菌emb B基因306位点突变与乙胺丁醇(EMB)药敏表型的关系,306位点突变与耐多药的关系。方法采用绝对浓度法和反向点杂交法对临床分离的447株结核分枝杆菌分别检测EMB药敏表型和emb B基因306位点突变情况。结果绝对浓度法EMB耐药39株,EMB敏感但耐其他药93株,全敏感315株;其中耐多药72株,非耐多药375株;应用反向点杂交法,39株EMB耐药组检出26株emb B基因306位点突变。306位点突变率在EMB耐药组(4.00%)、EMB敏感但耐其他药组(23.66%)、全敏感组(0.00%)间差异均有统计学意义;在耐多药组(45.83%)和非耐多药组(4.00%)间差异有统计学意义(P<0.05)。EMB绝对浓度法药敏试验与耐药基因检测结果经Kappa检验分析Kappa=0.5548小于0.75。rop B、kat G和emb B基因306位点任一突变代表基因型耐多药与耐多药表型符合率为95.83%。结论结核分枝杆菌emb B基因306位点突变与EMB耐药性中度相关,作为EMB耐药的分子标志值得商榷,emb B基因306位点突变预示耐多药的可能,EMB耐药可能还存在其他未知的耐药机制。Objective To determine the association between emb B mutation at codon 306 and drug resistance and multidrug resistance（MDR） in Mycobacterium tuberculosis for ethambutol（EMB）. Method EMB susceptibility phenotype and emb B mutation at codon 306 were determined by absolute concentration drug susceptibility test and reverse dot blot hybridization assay, respectively, 447 MTB strains. Results There were 39 strains EMB-resistant, 93 strains of EMBsensitive but resistant to other drugs, 315 strains sensitive to four drugs. 72 strains were MDR, 375 strains were nonMDR;26 out of 39 EMB-resistant strains had mutation located in codon 306 of emb B. The mutation rate of the emb B306 sites was statistically significant differences（P〈0.05） between the EMB resistance group（66.67%）, EMB sensitivity except resistant to other drug groups（23.66%） and the total susceptible group（0%）;There were statistically significant differences（P〈0.05） between the MDR groups（45.83%） and the non-MDR groups（4.00%）; The Kappa value between EMB absolute concentration of drug sensitivity test results and drug resistance gene results were 0.5548,less than 0.75.Among rop B, kat G and emb B, mutations at gene 306 locus, the coincidence rate were 95.83% between MDR genetype and MDR phenotype. Conclusion emb B mutation at codon 306 is moderately related to EMB resistance in Mycobacterium tuberculosis; mutation at codon 306 could not be the EMB resistant molecular marker; mutation at codon306 suggests the presence of multidrug-resistant possibility; EMB resistance may be also caused by other unknown mechanism.

关 键 词：结核分枝杆菌 乙胺丁醇 药敏表型 基因突变 

分 类 号：R378.91[医药卫生—病原生物学]