Mechanisms of variable p44 expression by Anaplasma phagocytophilum

Mechanisms of variable p44 expression by Anaplasma phagocytophilum
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DOI:
10.1128/iai.71.10.5650-5661.2003
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发表时间:
2003-10-01
影响因子:
3.1
通讯作者:
Zhi, N
Zhi, N
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Q;Rikihisa, Y;Zhi, N

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人类粒细胞内细菌嗜吞噬细胞无形体促进 P44 的变异,P44 是由 p44 多基因家族编码的表面暴露蛋白。在本研究中,鉴定了 4 个嗜吞噬细胞菌株中特定的 p44 基因表达位点,并确定每个菌株均由 tr1、omp-1X、omp-1N 和 p44 四个串联基因组成。在 W 上游发现了一个推定的 sigma(70) 型启动子。p44 基因包括一个中央高变区,两侧是保守区域。 p44 表达基因座中的高变区序列是重复的,并且无论表达状态如何,在菌株 NY-37 的低传代和高传代细胞培养物中的另一个基因座上都是保守的。当我们在 NY-37 和 HZ 菌株基因组的表达基因座和其他基因座内,在 cDNA 水平上比较 p44 序列时,没有发现高变区存在显着差异。类似地,在从患者和菌株 NY-31、NY-36 和 NY-37 的各种培养物中分离的 cDNA 中,发现每个菌株内各种 p44 的 450 个推导氨基酸序列的高变区是相同的,菌株 HZ 基因组中的 p44 序列也是相同的。这些数据表明,p44 表达基因座水平上的 p44 序列变异是通过整个(非节段)p44 高变区(包括具有从保守供体 p44 基因组基因座之一复制的相应序列的侧翼区域)的单向转换而发生的。数据表明高变区内的 p44 抗原库受到限制。
The human intragranulocytic bacterium Anaplasma phagocytophilum promotes variation of P44s, which are surface-exposed proteins encoded by a p44 multigene family. In the present study, the specific p44 gene expression loci in four strains of A. phagocytophilum were identified and it was determined that each consisted of four tandem genes, tr1, omp-1X, omp-1N, and p44. A putative sigma(70)-type promoter was found upstream of W. The p44 genes include a central hypervariable region flanked by conserved regions. The hypervariable region sequence in the p44 expression locus was duplicated and, regardless of the expression status, conserved at another locus in both low- and high-passage cell cultures of strain NY-37. No significant differences in the hypervariable region were found when we compared p44 sequences, at the level of cDNA, within the expression locus and within other loci in the genomes of strains NY-37 and HZ. Similarly, in cDNA isolated from patients and from assorted cultures of strains NY-31, NY-36, and NY-37, hypervariable regions of 450 deduced amino acid sequences of various p44s within each strain were found to be identical, as were those of p44 sequences in the genome of strain HZ. These data suggest that variations in p44 sequences at the level of the p44 expression locus occur through unidirectional conversion of the entire (nonsegmental) p44 hypervariable region including flanking regions with a corresponding sequence copied from one of the conserved donor p44 genomic loci. The data suggest that the p44 antigenic repertoire within the hypervariable region is restricted.