Group B streptococci escape host immunity by deletion of tandem repeat elements of the alpha C protein
Group B streptococci escape host immunity by deletion of tandem repeat elements of the alpha C protein
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DOI：
10.1073/pnas.93.9.4131
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发表时间：
1996-04-30
影响因子：
11.1
通讯作者：
Kasper, DL
中科院分区：
文献类型：
--
作者：
Madoff, LC;Michel, JL;Kasper, DL
B族链球菌（GBS）是新生儿败血症、肺炎和脑膜炎的最常见原因。α C蛋白是一种表面相关抗原;该蛋白的基因（bca）含有一系列串联重复序列（每个编码82个aa），这些重复序列在核苷酸水平上相同，并表达保护性表位。我们以前曾报道，GBS分离物从两个14人的母亲和新生儿对不同的α C蛋白中所含的重复的数量;在这两对中，α C蛋白的新生儿分离物的分子大小较小。我们现在通过PCR证明新生儿分离株含有较少的串联重复序列。母体分离株在α C蛋白特异性抗血清存在下易受调理吞噬杀伤，而差异新生儿分离株增殖。为了进一步研究这一现象，开发了一种动物模型。用α C蛋白的抗血清被动免疫的成年小鼠用表达α C蛋白的GBS菌株攻击。从这些小鼠中分离出的GBS的脾脏显示出bca突变的高频率，最常见的是重复数的减少。来自非免疫小鼠的分离株没有改变。在重复区域中观察到的自发缺失频率要低得多（6 × 10 - 4）;因此，该区域的缺失在特异性抗体压力下被选择，并且似乎降低了生物体对α C蛋白特异性抗体杀伤的敏感性。这种抗原变异机制可能提供了GBS逃避宿主免疫的手段。
Group B streptococci (GBS) are the most common cause of neonatal sepsis, pneumonia, and meningitis. The alpha C protein is a surface-associated antigen; the gene (bca) for this protein contains a series of tandem repeats (each encoding 82 aa) that are identical at the nucleotide level and express a protective epitope. We previously reported that GBS isolates from two of 14 human maternal and neonatal pairs differed in the number of repeats contained in their alpha C protein; in both pairs, the alpha C protein of the neonatal isolate was smaller in molecular size. We now demonstrate by PCR that the neonatal isolates contain fewer tandem repeats. Maternal isolates were susceptible to opsonophagocytic killing in the presence of alpha C protein-specific antiserum, whereas the discrepant neonatal isolates proliferated. An animal model was developed to further study this phenomenon. Adult mice passively immunized with antiserum to the alpha C protein were challenged with an alpha C protein-expressing strain of GBS. Splenic isolates of GBS from these mice showed a high frequency of mutation in bca-most commonly a decrease in repeat number. Isolates from nonimmune mice were not altered. Spontaneous deletions in the repeat region were observed at a much lower frequency (6 x 10(-4)); thus, deletions in that region are selected for under specific antibody pressure and appear to lower the organism's susceptibility to killing by antibody specific to the alpha C protein. This mechanism of antigenic variation may provide a means whereby GBS evade host immunity.