European human granulocytic anaplasmosis is caused by a subcluster of Anaplasma phagocytophilum Ecotype I

<i>Anaplasma phagocytophilum</i> causes human granulocytic anaplasmosis. However, despite its ubiquitous presence in animals and ticks, human cases are rarely reported in Europe. We generated genetic data from <i>A. phagocytophilum</i> from patients and compared them with sequences from wild and domestic animals to assess the zoonotic potential of the respective genotypes. The genomic sequence of an <i>A. phagocytophilum</i> isolate obtained from a Slovenian patient was determined. We also sequenced a <i>groEL</i>-gene fragment of eight isolates from human patients from France and Poland. The <i>A. phagocytophilum</i> genome from the Slovenian patient was more closely related to isolates from dogs than from sheep. Using <i>groEL</i>-based typing, isolates from humans were found within a distinct subcluster of <i>A. phagocytophilum</i> Ecotype I. This subcluster was defined as zoonotic. Strains from dogs, horses, cats, foxes, wolves, and wild boar were significantly overrepresented in this branch. Variants outside this subcluster were more abundant and found in a wider variety of domestic and wild animals, most notably ruminants. A similar pattern was observed for the MLST analyses targeting seven housekeeping genes. Human anaplasmosis in Europe is associated with a specific subcluster of <i>A. phagocytophilum</i> Ecotype I, which is not primarily associated with ruminants, but rather with dogs, horses, cats, carnivores, wild boar and hedgehogs. Our findings provide a reasonable explanation for the discrepancy between the omnipresence of <i>A. phagocytophilum</i> in the environment and the limited number of reported human cases. We recommend taking this genetic sub-clustering into account for future risk assessments.