Comparative Tropical Medicine and Parasitology, Ludwig-Maximilians-Universität München, Leopoldstrasse 5, 80802, Munich, Germany.
Institute of Infectology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17943, Greifswald-Insel Riems, Germany.
Parasit Vectors. 2023 Aug 16;16(1):289. doi: 10.1186/s13071-023-05900-3.
The zoonotic intracellular alpha-proteobacterium Anaplasma phagocytophilum is a tick-transmitted pathogen. The associations between vertebrate reservoirs and vectors are described as wide-ranging, and it was previously shown that the pathogenicity of A. phagocytophilum differs depending on the combination of pathogen variant and infected host species. This leads to the question of whether there are variations in particular gene loci associated with different virulence. Therefore, this study aims at clarifying existing host-variant combinations and detecting possible reservoir hosts. To understand these interactions, a complex toolset for molecular epidemiology, phylogeny and network theory was applied.
Sequences of up to four gene loci (msp4, msp2, groEL and 16S rRNA) were evaluated for different isolates from variable host species, including, for example, dogs, cattle and deer. Variant typing was conducted for each gene locus individually, and combinations of different gene loci were analysed to gain more detailed information about the genetic plasticity of A. phagocytophilum. Results were displayed as minimum spanning nets and correlation nets.
The highest diversity of variants for all gene loci was observed in roe deer. In cattle, a reduced number of variants for 16S rRNA [only 16S-20(W) and 16S-22(Y)] but multiple variants of msp4 and groEL were found. For dogs, two msp4 variants [m4-20 and m4-2(B/C)] were found to be linked to different variants of the other three gene loci, creating two main combinations of gene loci variants. Cattle are placed centrally in the minimum spanning net analyses, indicating a crucial role in the transmission cycles by possibly bridging the vector-wildlife cycle to infections of humans and domestic animals. The minimum spanning nets confirmed previously described epidemiological cycles of the bacterium in Europe, showing separation of variants originating from wildlife animals only and a set of variants shared by wild and domestic animals.
In this comprehensive study of 1280 sequences, we found a high number of gene variants only occurring in specific hosts. Additionally, different hosts show unique but also shared variant combinations. The use of our four gene loci expand the knowledge of host-pathogen interactions and may be a starting point to predict future spread and infection risks of A. phagocytophilum in Europe.
人畜共患的细胞内α-变形菌嗜吞噬细胞无形体是一种蜱传播的病原体。脊椎动物宿主和媒介之间的联系被描述为广泛的，并且先前已经表明，嗜吞噬细胞无形体的致病性因病原体变体和感染宿主物种的组合而异。这就提出了一个问题，即是否存在与不同毒力相关的特定基因座的变异。因此，本研究旨在阐明现有的宿主-变体组合并检测可能的宿主。为了理解这些相互作用，应用了用于分子流行病学、系统发育和网络理论的复杂工具集。
评估了来自不同宿主物种（例如狗、牛和鹿）的不同分离株的多达四个基因座（msp4、msp2、groEL 和 16S rRNA）的序列。对每个基因座分别进行变体分型，并分析不同基因座的组合，以更详细地了解嗜吞噬细胞无形体的遗传可塑性。结果以最小生成网络和相关网络显示。
所有基因座的变体多样性最高的是狍。在牛中，16S rRNA 的变体数量减少[仅 16S-20(W)和 16S-22(Y)]，但发现了多个 msp4 和 groEL 变体。对于狗，发现两种 msp4 变体[m4-20 和 m4-2(B/C)]与其他三个基因座的不同变体相关联，形成了两个主要的基因座变体组合。牛在最小生成网络分析中处于中心位置，表明它们在通过可能将媒介-野生动物循环桥接到人类和家畜感染中在传播循环中起着关键作用。最小生成网络证实了该细菌在欧洲以前描述的流行病学循环，显示出仅源自野生动物的变体分离和一组由野生动物和家畜共享的变体。
在这项对 1280 个序列的综合研究中，我们发现只有在特定宿主中才存在大量基因变体。此外，不同的宿主具有独特但也共享的变体组合。使用我们的四个基因座扩展了宿主-病原体相互作用的知识，并可能成为预测未来欧洲嗜吞噬细胞无形体传播和感染风险的起点。
