Vidal Vincent, Cutler Sally, Scragg Ian G, Wright David J M, Kwiatkowski Dominic
Molecular Infectious Disease Group, Weatherall Institute of Molecular Medicine, Oxford, UK.
BMC Infect Dis. 2002 Oct 14;2:25. doi: 10.1186/1471-2334-2-25.
We report the characterisation of the variable large protein (vlp) gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever.
The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1B. recurrentis A1 gene in both this and other isolates.
This isolate was found to carry silent and expressed copies of the vlp1B. recurrentis A1 gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1B. recurrentis A17 on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters.
Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates.
我们报告了由回归热疏螺旋体临床分离株A1表达的可变大蛋白(vlp)基因的特征;回归热疏螺旋体是危及生命的虱传回归热的病原体。
对该分离株的主要vlp蛋白进行了表征,并构建了一个DNA探针。将其与标准分子方法一起用于确定回归热疏螺旋体A1的vlp1B基因在该分离株和其他分离株中的位置。
发现该分离株分别在54 kbp和24 kbp的质粒上携带回归热疏螺旋体A1的vlp1B基因的沉默拷贝和表达拷贝,而另一个分离株A17仅在一个54 kbp的质粒上携带回归热疏螺旋体A17的沉默vlp1B。沉默的vlp1和表达的vlp1具有相同的成熟蛋白编码区,但具有不同的5'区域,两者都包含不同的潜在脂蛋白前导序列。在回归热疏螺旋体的A1分离株中仅转录一种形式的vlp1,然而该vlp1基因的两个5'上游序列都具有细菌启动子的特征。
综合这些结果表明,回归热疏螺旋体的抗原变异可能是由于可变大蛋白和小蛋白基因在脂蛋白前导序列和成熟蛋白编码区之间的连接处发生重组所致。然而,这个假设模型需要通过进一步鉴定其他回归热疏螺旋体分离株中表达的和沉默的变异蛋白基因来验证。