Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus

Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus
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DOI:
10.1128/aac.40.7.1676
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发表时间:
1996-07-01
影响因子:
4.9
通讯作者:
Bottger, EC
Bottger, EC
中科院分区:
医学2区
文献类型:
--
作者:
Wallace, RJ;Meier, A;Bottger, EC

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龟分枝杆菌和分枝杆菌对克拉霉素的耐药性。1990年至1995年间接受检测的800名患者中,有18名(2.3%)出现脓肿。耐药菌株的患者患有播散性疾病或慢性肺病,耐药菌株在克拉霉素单药治疗后恢复,对编码23S rRNA肽基转移酶区域的基因进行测序,发现2058位腺嘌呤(38%)或2059位腺嘌呤(62%)存在点突变。在前13名患者的20个复发分离株中有20个。经脉冲场凝胶电泳或随机扩增多态性DNA聚合酶链反应(RAPD)分析,初发和复发分离株的DNA带型完全相同,M。chelonae和M.发现分枝杆菌分离株仅具有rRNA操纵子的单个染色体拷贝,因此使其易于发生单步突变。因此,这些快速生长的分枝杆菌种属中的克拉霉素耐药性与编码238 rRNA的基因中的点突变有关,并发生在有限的临床模拟中,但在1995年检测的几乎5%的分离株中鉴定出。
Resistance to clarithromycin among isolates of Mycobacterium chelonae and M. abscessus was observed in 18 of 800 (2.3%) patients tested between 1990 and 1995. Patients whose isolates were resistant had either disseminated disease or chronic lung disease, and the resistant isolates were recovered after clarithromycin monotherapy, Sequencing of the gene coding for the 23S rRNA peptidyltransferase region revealed a point mutation involving adenine at position 2058 (38%) or adenine at position 2059 (62%) in 20 of 20 relapse isolates from the first 13 patients identified. By pulsed-field gel electrophoresis or random amplified polymorphic DNA PCR, initial and relapse isolates were shown to have identical DNA patterns, M. chelonae and M. abscessus isolates were found to have only a single chromosomal copy of the rRNA operon, thus making them susceptible to single-step mutations, Thus, clarithromycin resistance in these species of rapidly growing mycobacteria relates to a point mutation in the gene coding for 238 rRNA and occurs in limited clinical simulations, but was identified in almost 5% of isolates tested in 1995.