结核分枝杆菌临床分离株链霉素耐药相关基因rpsL和rrs突变的研究

Study on mutation of rpsL and rrs genes associated with streptomycin resistance in mycobacterium tuberculosis isolates

目的链霉素在结核病治疗中作为一线药物广泛使用,我国已经使用50年以上。本文主要研究结核分枝杆菌链霉素耐药基因rpsL和rrs基因突变检测对链霉素耐药的相关性。方法 205株结核分枝杆菌临床分离株(经常规方法证实,125株为链霉素耐药,80株为敏感),测定链霉素最小抑菌浓度(MIC),测序法检测rpsL和rrs基因突变。结果 84%(105/125)的链霉素耐药株携有rpsL或/和rrs基因突变,其中rpsL基因突变占大多数(76.8%,96/125)。对105株带有基因突变的菌株的分析表明,rpsL,rrs基因的突变类型与MIC之间未见密切关系。80株敏感株未检出基因突变。结论结核分支杆菌链霉素耐药相关基因rpsL和rrs突变在结核分枝杆菌链霉素耐药中起主要作用。

Objective As a first - line anti - tuberculosis, streptomycin has been widely used more than 50 years in tuberculo- sis treatment in China. This study aimed to find the association between rpsL and rrs gene mutation and Streptomycin resistance. Methods Two hundred and five clinical M. tuberculosis isolates （ 125 streptomycin - resistant strains and 80 streptomycin - susceptible strains） were collected to determine the MIC of streptomycin, and the mutation of rpsL and rrs was detected by DNA sequencing. Results Mutation of rpsL or rrs were found in 105 streptomycin - resistant isolates （ 105/125, 84% ）, with rpsL mutation as dominant gene mutation（76.8%, 96/125）. MIC of 105 mutant isolates revealed that there was no close correlation between mutation types and streptomycin resistance level. No mutation was found in all the susceptible isolates. Conclusion The mutation of rpsL and rrs genes may play an important role in streptomycin - resistant Mycobacteriun tuberculo- sis isolates.