Jadaun G P S, Das Ram, Upadhyay Prashant, Chauhan D S, Sharma V D, Katoch V M
Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Indian Council of Medical Research, Dr M. Miyazaki Marg, Tajganj, Agra 282001, India.
Int J Antimicrob Agents. 2009 May;33(5):483-6. doi: 10.1016/j.ijantimicag.2008.10.017. Epub 2008 Dec 27.
In the present study, ethambutol (EMB) resistance-associated mutations were characterised in the embCAB genes of clinical isolates of Mycobacterium tuberculosis (MTB) collected in India. Thirty MTB isolates were tested for their susceptibility to first-line antitubercular drugs using the Löwenstein-Jensen proportion method, and EMB minimum inhibitory concentrations of MTB isolates were determined by the resazurin microtitre assay. Sequencing of various regions of the embCAB genes was performed to identify EMB resistance-associated mutations. Mutations of embB306 were detected in 15 of 23 EMB-resistant MTB isolates. Three EMB-resistant isolates had mutations at codon 270 of the embC gene, two of which also harboured embB306 mutations. No mutation was identified in the embA gene. All seven EMB-sensitive MTB isolates had the wild-type embCAB sequence. In summary, embB306 mutations were associated with EMB resistance, and mutation at codon 270 of the embC gene may contribute to high-level EMB resistance in some MTB isolates.
在本研究中,对在印度收集的结核分枝杆菌(MTB)临床分离株的embCAB基因中与乙胺丁醇(EMB)耐药相关的突变进行了特征分析。采用罗氏培养基比例法对30株MTB分离株进行一线抗结核药物敏感性检测,并用刃天青微量滴定法测定MTB分离株的EMB最低抑菌浓度。对embCAB基因的各个区域进行测序以鉴定与EMB耐药相关的突变。在23株对EMB耐药的MTB分离株中,有15株检测到embB306突变。3株对EMB耐药的分离株在embC基因的第270密码子处发生突变,其中2株还存在embB306突变。在embA基因中未发现突变。所有7株对EMB敏感的MTB分离株均具有野生型embCAB序列。总之,embB306突变与EMB耐药相关,embC基因第270密码子处的突变可能在某些MTB分离株中导致高水平的EMB耐药。