Alcaide F, Pfyffer G E, Telenti A
Institute for Medical Microbiology, University of Berne, Switzerland.
Antimicrob Agents Chemother. 1997 Oct;41(10):2270-3. doi: 10.1128/AAC.41.10.2270.
The mycobacterial embCAB operon encodes arabinosyl transferases, putative targets of the antimycobacterial agent ethambutol (EMB). Mutations in embB lead to resistance to EMB in Mycobacterium tuberculosis. The basis for natural, intrinsic resistance to EMB in nontuberculous mycobacteria (NTM) is not known; neither is the practical implication of resistance to EMB in the absence of embB mutations in M. tuberculosis well understood. The conserved embB resistance-determining region (ERDR) of a collection of 13 strains of NTM and 12 EMB-resistant strains of M. tuberculosis was investigated. Genotypes were correlated with drug susceptibility phenotypes. High-level natural resistance to EMB (MIC, . or =64 microg/ml) was associated with a variant amino acid motif in the ERDR of M. abscessus, M. chelonae, and M. leprae. Transfer of the M. abscessus emb allele to M. smegmatis resulted in a 500-fold increase in the MICs. In M. tuberculosis, embB mutations were associated with MICs of > or =20 microg/ml while resistance not associated with an ERDR mutation generally resulted in MICs of < or =10 microg/ml. These data further support the notion that the emb region determines intrinsic and acquired resistance to EMB and might help in the reassessment of the current recommendations for the screening and treatment of infections with EMB-resistant M. tuberculosis and NTM.
分枝杆菌embCAB操纵子编码阿拉伯糖基转移酶，是抗分枝杆菌药物乙胺丁醇（EMB）的假定作用靶点。embB基因的突变会导致结核分枝杆菌对EMB产生耐药性。非结核分枝杆菌（NTM）对EMB天然固有耐药的机制尚不清楚；同样，在结核分枝杆菌中，在不存在embB突变的情况下对EMB耐药的实际意义也未得到充分理解。对13株NTM菌株和12株耐EMB结核分枝杆菌菌株的保守embB耐药决定区（ERDR）进行了研究。将基因型与药物敏感性表型进行关联分析。脓肿分枝杆菌、龟分枝杆菌和麻风分枝杆菌的ERDR中一种变异氨基酸基序与对EMB的高水平天然耐药（MIC，≥64μg/ml）相关。将脓肿分枝杆菌的emb等位基因转移至耻垢分枝杆菌，导致MIC增加500倍。在结核分枝杆菌中，embB突变与MIC≥20μg/ml相关，而与ERDR突变无关的耐药通常导致MIC≤10μg/ml。这些数据进一步支持了emb区域决定对EMB的固有和获得性耐药这一观点，并可能有助于重新评估目前针对耐EMB结核分枝杆菌和NTM感染的筛查和治疗建议。
