结核分枝杆菌抗原PE35和PPE68基因多态性的初步研究  

Polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis

作　　者：仇艳[1,2] 蒋毅[1,2] 刘海灿[1,2] 李马超[1,2] 万康林[1,2] 

机构地区：[1]中国疾病预防控制中心传染病预防控制所传染病预防控制国家重点实验室,北京102206 [2]感染性疾病诊治协同创新中心,杭州310003

出　　处：《疾病监测》2015年第7期539-545,共7页Disease Surveillance

基　　金：国家自然科学基金(No.81401647);国家科技重大专项(No.2013ZX10003006;2013ZX10003002-001)~~

摘　　要：目的为研究结核分枝杆菌RD1区编码PE/PPE蛋白家族中的PE 35和PPE 68基因的多态性,并评估其基因多态性对免疫识别的影响。方法笔者从本实验室保存的来自国内不同地区的2346株结核分枝杆菌复合群临床分离株中,选取代表不同Spoligotyping类型的161株临床分离结核分枝杆菌菌株,基因扩增后进行序列比对,比较其在T细胞抗原表位的差异。结果在161株菌株中,23株显示有PE 35基因多态性,8株有PPE 68基因多态性。在PE 35基因中,除了菌株JL06018的突变外的其余突变都导致其T细胞抗原表位的改变。PPE 68基因中,62个T细胞表位中有58个(占93.5%)发生了改变。非北京家族PE 35基因的突变率明显高于北京家族(P<0.05),而PPE 68基因突变虽是非北京家族高于北京家族,但差异无统计学意义。结论 PE 35和PPE 68的编码基因存在明显的多态性,并很有可能导致蛋白功能的明显改变。此外,这2个蛋白的人类T细胞表位是高度可变的,提示这2种蛋白可能通过参与分化选择来逃避宿主免疫。北京家族可能比非北京家族更容易被宿主T细胞识别,进而更容易传播。Objective To understand the polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis and evaluate the influence of the polymorphism on immune recognition. Methods A total of 161 clinical M. tuberculosis strains isolated in China w ere selected and comparative sequence analysis of PE 35 and PPE 68 genes w as conducted after amplification. Results Among the 161 M. tuberculosis strains,23 show ed the polymorphism in the gene sequence of PE 35 and 8 show ed the polymorphisms in the gene sequence of PPE 68. The mutations in all the PE 35 gene,except that in JL06018,influenced the T cell epitopes. In PPE 68 gene,58 of 62 T cell epitopes changed,accounting for 93. 5%. The mutation rate of PE 35 gene in non-Beijing family strains w as significantly higher than that in Beijing family strains（ P〈0. 05）. Although the mutation rate of PPE 68 gene in non-Beijing family strains w as higher than that in Beijing family strains,the difference had no statistical significance. Conclusion Polymorphisms w ere observed in PE 35 and PPE 68 genes,w hich might resulting in the drastic changes in the functions of these proteins and influence the virulence of the strains. Beijing family strains are more likely to be recognized than non-Beijing family strains by host T cell in PE 35 gene,w hich facilitates the spread of Beijing family strains.

关 键 词：多态性 结核分枝杆菌 PE 35 PPE 68 

分 类 号：R378.911[医药卫生—病原生物学]