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结核分枝杆菌链霉素耐药基因突变特征分析

Mutation characteristics of streptomycin resistance genes in Mycobacterium tuberculosis

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【作者】 陈伊翁琼琳孟繁荣

【Author】 CHEN Yi;WENG Qionglin;MENG Fanrong;Bao’an District Chronic Disease Control Institute,Shenzhen;

【机构】 深圳市宝安区慢性病防治院广州市胸科医院

【摘要】 目的了解广东地区链霉素耐药结核分枝杆菌rpsL、rrs基因突变特征。方法对137株链霉素耐药、166株链霉素敏感的结核分枝杆菌临床分离株应用聚合酶链式反应技术(PCR)扩增rpsL、rrs基因片段,并进行测序、分析比对。结果 137株链霉素耐药菌株中,118株存在rrs或者rpsL基因突变,突变率86.13%;其中92株存在rpsL基因突变(突变率为67.15%),主要分布在43位氨基酸(70株)与88位氨基酸(20株),其中43位氨基酸突变类型为K→R(AAG→AGG,49.64%)和K→T(AAG→ACG,1.46%),88位氨基酸突变类型为K→R(AAG→AGG,13.14%)、K→T(AAG→ACG,0.73%)和K→Q(AAG→CAG,0.73%),并有2株存在39、43位氨基酸的联合突变,即T→T(ACC→ACT)联合K→T(AAG→ACG)突变(1.46%);47株存在rrs基因突变(突变率为34.31%),包括8种核苷酸突变,主要分布在1401位A→G(13.14%)、514位A→C(8.76%)、517位C→T(6.57%),2株存在514、1401位核苷酸A→C;A→G的联合突变;15株存在rpsL与rrs基因的同时突变;166株链霉素敏感菌株中,7株存在rpsL基因突变,13株存在rrs基因突变。结论广东地区链霉素耐药结核分枝杆菌株的rpsL、rrs基因突变具有其自身特点,存在地域差异。

【Abstract】 Objective To understand the mutation characteristics of rpsL and rrs genes in streptomycin-resistant Mycobacterium tuberculosis in Guangdong area.Methods rpsL and rrs gene fragments in 137 streptomycin-resistant and 166 streptomycin-sensitive clinical isolates of Mycobacterium tuberculosis were amplified by PCR and sequenced and compared.Results Among 137 strains of streptomycin-resistant strains,118 strains had rrs or rpsL gene mutations,and the mutation rate was 86.13%;92 strains had rpsL gene mutations with the mutation rate of 67.15%,and were mainly distributed at amino acid 43(70 strains)and amino acid 88(20 strains).The amino acid 43 mutations were K→R(AAG→AGG,49.64%)and K→T(AAG→ACG,1.46%),and amino acid 88 mutation was K→R(AAG→AGG,13.14%),K→T(AAG→ACG,0.73%)and K→Q(AAG→CAG,0.73%),and there were the joint mutations of amino acid 39 and 43 in two strains:T→T(ACC→ACT)combined K→T(AAG→ACG)mutations(1.46%);47 strains had rrs gene mutations(mutation rate:34.31%),including 8nucleotide mutations,mainly distributed at position 1401 A→G(13.14%),514 A→C(8.76%),517 C→T(6.57%);2 strains had nucleotides co-mutation at position 514 and 1401(A→C;A→G);15 strains had the simultaneous mutation of rpsL and rrs;among 166 strains of streptomycin-sensitive strains,7 had rpsL gene mutations and 13 had rrs gene mutations.Conclusion sThe rpsL and rrs gene mutations of streptomycin-resistant Mycobacterium tuberculosis strains in Guangdong region have their own characteristics,and there are regional differences.

【基金】 广州市医药卫生科技项目(No.20151A011036);深圳市宝安区医疗卫生基础研究项目(No.2017JD168)
  • 【文献出处】 中国热带医学 ,China Tropical Medicine , 编辑部邮箱 ,2018年06期
  • 【分类号】R378.911
  • 【被引频次】4
  • 【下载频次】171
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