宁波地区耐多药结核分枝杆菌乙胺丁醇耐药embB基因突变研究

Studies on the ethambutol resistance related embB mutation of multidrug-resistant Mycobacterium tuberculosis in Ningbo

目的分析宁波地区耐多药结核分枝杆菌(multiple drug-resistant tuberculosis,MDR-TB)临床分离株的embB基因突变特征,探讨MDR-TB对乙胺丁醇(ethambutol,EMB)耐药的产生与embB基因突变的关系。方法采用比例法对MDR-TB临床分离株进行EMB敏感性检测,应用DNA直接测序法检测MDR-TB的embB基因突变情况。结果 106株MDR-TB临床分离株中有49株(46.23%)对EMB耐药,57株(53.77%)对EMB敏感,59株(55.66%)发生了embB基因突变。在49株EMB耐药菌株中,embB基因突变的菌株为34株(69.39%),在57株EMB敏感菌株中,embB基因突变的菌株为25株(43.86%),EMB耐药菌株中的embB基因突变率高于敏感菌株(χ2=6.958,P<0.05)。embB基因突变类型有embB306,embB354,embB406,以embB306突变最多。embB306在EMB耐药菌株中的突变率高于EMB敏感菌株(χ2=6.275,P<0.05)。embB基因和embB306位点检测EMB耐药的敏感度、特异度和准确度分别为69.39%、56.14%、62.26%和61.22%、63.16%、62.26%。结论宁波地区MDR-TB对EMB耐药形势较为严峻,embB基因突变与MDR-TB对EMB耐药相关。

Objective To explore the association between embB mutation of multidrug-resistant Mycobacterium tuberculosis（MDR-TB）and ethambutol（EMB）resistance. Methods Proportion method was used to test the EMB resistance of 106 MDR-TB strains and gene sequencing was performed to identify the mutation of embBgene.The association between embB mutation and the EMB resistance was analyzed with chi-square test.Results Out of 106 strains of MDR-TB,49 were resistant to EMB（46.23%）,57 were sensitive to EMB（53.77%）.embB mutation was identified in 59 MDR-TB strains（55.66%）.embB mutation was found in 34 strains（69.39%）of 49 EMB resistant ones and 25（43.86%）of 57 EMB sensitive strains.The mutation rate of embB was much higher in EMB resistant strains than in EMB sensitive strains（χ2=6.958,P 0.05）.embB306 was the major mutation loci,and this mutation rate was much higher in EMB resistant strains than in EMB sensitive strains（χ2=6.275,P〈0.05）.The sensitivity,specificity and accuracy of EMB susceptibility test were 69.39%,56.14%,62.26%for embB mutation and 61.22%,63.16%,62.26%for embB306 loci respectively. Conclusions Many MDR-TB clinical isolates are resistant to EMB and embB mutation is closely associated with EMB resistance.