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Structure of the Expression Site Reveals Global Diversity in MSP2 (P44) Variants in Anaplasma phagocytophilum

机译:表达位点的结构揭示吞噬嗜浆细胞中MSP2(P44)变体的全局多样性。

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Anaplasma phagocytophilum, a recently reclassified bacteria in the order Rickettsiales, infects many different animal species and causes an emerging tick-borne disease of humans. The genome contains a large number of related genes and gene fragments encoding partial or apparently full-length outer membrane protein MSP2 (P44). Previous data using strains isolated from humans in the United States suggest that antigenic diversity results from RecF-mediated conversion of a single MSP2 (P44) expression site by partially homologous donor sequences. However, whether similar mechanisms operate in naturally infected animal species and the extent of global diversity in MSP2 (P44) are unknown. We analyzed the structure and diversity of the MSP2 (P44) expression site in strains derived from the United States and Europe and from infections of different animal species, including wildlife reservoirs. The results show that a syntenic expression site is present in all strains of A. phagocytophilum investigated. This genomic locus contained diverse MSP2 (P44) variants in all infected animals sampled, and variants also differed at different time points during infection. Although similar variants were found among different populations of U.S. origin, there was little sequence identity between U.S. strain variants (including genomic copies from a completely sequenced U.S. strain) and expression site variants infecting sheep and dogs in Norway and Sweden. Finally, the possibility that combinatorial mechanisms can generate additional diversity beyond the basic donor sequence repertoire is supported by the observation of shared sequence blocks throughout the MSP2 (P44) hypervariable region in reservoir hosts. These data suggest similar genetic mechanisms for A. phagocytophilum variation in all hosts but worldwide diversity of the MSP2 (P44) outer membrane protein.
机译:吞噬细胞无浆质子是一种最近被重新分类为立克次氏体的细菌,它感染了许多不同的动物物种,并引起了由人传播的由tick传播的疾病。基因组包含大量相关基因和编码部分或显然全长外膜蛋白MSP2(P44)的基因片段。在美国使用从人类分离的菌株的先前数据表明,抗原多样性是由RecF介导的部分同源供体序列对单个MSP2(P44)表达位点的转化所致。但是,尚不清楚类似的机制是否在自然感染的动物物种中起作用,以及MSP2(P44)中的全球多样性程度。我们分析了MSP2(P44)表达位点在来自美国和欧洲以及不同动物物种(包括野生动植物水库)感染的菌株中的结构和多样性。结果表明在所有 A菌株中都存在同义表达位点。吞噬细胞。在所有采样的受感染动物中,该基因组基因座均包含多种MSP2(P44)变异体,并且变异在感染期间的不同时间点也有所不同。尽管在不同的美国血统人群中发现了相似的变体,但在挪威和瑞典,美国的菌株变体(包括来自完全测序的美国菌株的基因组拷贝)与感染绵羊和狗的表达位点变体之间几乎没有序列同一性。最后,通过观察储层宿主中整个MSP2(P44)高变区的共享序列区块,可以证明组合机制可以产生超出基本供体序列库以外的其他多样性的可能性。这些数据表明了 A的相似遗传机制。 MSP2(P44)外膜蛋白在所有寄主中都有嗜噬细胞的变化,但在全世界范围内却存在差异。

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