Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex
Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex
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DOI：
10.1128/aac.48.1.143-150.2004
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发表时间：
2004-01-01
影响因子：
4.9
通讯作者：
Pernodet, JL
中科院分区：
文献类型：
--
作者：
Buriánková, K;Doucet-Populaire, F;Pernodet, JL
结核分枝杆菌复合体(MTC)对包括大环内酯类在内的大多数抗生素的内在耐药性通常归因于分枝杆菌细胞壁的低通透性。然而，非结核分枝杆菌(NTM)比MTC成员对大环内酯类药物更敏感。对结核分枝杆菌基因组中大环内酯类耐药决定因素的搜索发现，存在一个编码假定的rRNA甲基转移酶的序列。该蛋白与Erm甲基转移酶相似，通过23S rRNA甲基化产生大环内酯-林可胺-链球菌素(MLS)抗性，命名为ErmMT。相应的基因ermMT(Erm37)存在于MTC的所有成员中，但在NTM物种中缺失。在一些牛分枝杆菌卡介苗疫苗株中，部分ermMT基因被缺失，例如巴斯德株，它缺乏Rd2区。巴斯德菌株对MLS抗生素敏感，而含有RD2区的MTC菌株对MLS抗生素耐药。在对大环内酯类药物敏感的污垢分枝杆菌和BCG巴斯德中，ermMT的表达使其对MLS产生耐药。比较了表达ermMT、srmA和Erme的红霉素分枝杆菌宿主菌株对红霉素的耐药性和核糖体亲和力，ErmMT与SrmA相似，符合MLS I型表型。这些结果表明，ermMT在MTC成员的内在大环内酯类耐药性中发挥了重要作用，并可能成为分枝杆菌中第一个通过靶向修饰而产生耐药性的基因。
The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria.