Ahmad S, Jaber A-A, Mokaddas E
Department of Microbiology, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Tuberculosis (Edinb). 2007 Mar;87(2):123-9. doi: 10.1016/j.tube.2006.05.004. Epub 2007 Feb 7.
Recent reports of embB306 mutations in ethambutol-resistant and ethambutol-susceptible drug-resistant strains of Mycobacterium tuberculosis have questioned the significance of these mutations in conferring resistance to ethambutol (EMB).
To determine the occurrence of embB306 mutations in all EMB-resistant and -susceptible drug-resistant M. tuberculosis strains isolated during a specified period at a single geographical location.
Twenty-five pansusceptible, all EMB-resistant and -susceptible M. tuberculosis strains resistant to other first-line drugs isolated in Kuwait during 2000-2003 were analyzed. The embB306 mutations were detected by PCR-restriction fragment length polymorphism and DNA sequencing. The PCR-based methods were also used for determining strain relatedness.
None of the pansusceptible M. tuberculosis strains contained a mutation at embB306. Fifteen of 50 (30%) EMB-resistant strains but only three of 122 (2%) EMB-susceptible isolates resistant to other first-line drugs contained a mutated embB306. The EMB-susceptible isolates with embB306 mutation were resistant to isoniazid plus other drug(s). The isolates carrying similar mutations were genotypically distinct strains.
The frequency of embB306 mutations in EMB-resistant strains compared to EMB-susceptible M. tuberculosis isolates resistant to other drugs was 15 times higher. Association of embB306 mutations in EMB-susceptible strains with isoniazid resistance and inherent problems associated with phenotypic EMB susceptibility testing suggest that these strains may actually be EMB-resistant.
近期关于结核分枝杆菌耐乙胺丁醇菌株和乙胺丁醇敏感耐药菌株中embB306突变的报道，对这些突变在赋予乙胺丁醇（EMB）耐药性方面的意义提出了质疑。
确定在单一地理位置特定时期分离出的所有耐EMB和对EMB敏感的耐药结核分枝杆菌菌株中embB306突变的发生率。
分析了2000年至2003年在科威特分离出的25株对所有药物敏感、所有耐EMB以及对其他一线药物耐药且对EMB敏感的结核分枝杆菌菌株。通过聚合酶链反应-限制性片段长度多态性和DNA测序检测embB306突变。基于聚合酶链反应的方法也用于确定菌株的相关性。
所有对药物敏感的结核分枝杆菌菌株在embB306处均未发生突变。50株耐EMB菌株中有15株（30%），但在122株对其他一线药物耐药且对EMB敏感的菌株中只有3株（2%）含有embB306突变。具有embB306突变的对EMB敏感的菌株对异烟肼加其他药物耐药。携带相似突变的菌株是基因分型不同的菌株。
与对其他药物耐药且对EMB敏感的结核分枝杆菌分离株相比，耐EMB菌株中embB306突变的频率高15倍。对EMB敏感菌株中embB306突变与异烟肼耐药性的关联以及与表型EMB敏感性检测相关的固有问题表明，这些菌株实际上可能是耐EMB的。
