Exploration of geographical population structure of Anaplasma phagocytophilum: Insights from 12 newly sequenced European human and bovine genomes assemblies

Anaplasma phagocytophilum is an obligate intracellular tick-borne bacterium widely distributed across the northern hemisphere. It is the causative agent of tick-borne fever in ruminants and human granulocytic anaplasmosis. The epidemiology of A. phagocytophilum infection differs markedly between the USA and Europe. In the USA, human granulocytic anaplasmosis represents an increasing public health concern, whereas infections in ruminants are rarely reported. In contrast, in Europe only sporadic human cases have been described, while infections in ruminants cause significant economic losses. Previous genomic studies based on limited datasets suggested genetic divergence between USA and European strains, but the small number of available genomes, particularly from Europe, limited robust conclusions. In this study, we report 12 new European A. phagocytophilum genomes, including four human-derived genomes and eight genomes from cattle. Using a capture-based short-read sequencing approach, we doubled the number of publicly available European genomes. In addition, systematic quality assessment of these public assemblies revealed variable genome completeness and the presence of contamination in several genomes. After curation of these datasets and inclusion of our 12 new sequenced genomes, comparative genomic analyses were performed using phylogenetic and population genetic approaches. Our results confirm a marked genetic divergence between European and USA strains. Hence, the capture-based short-read sequencing can be performed on samples from naturally infected humans and ruminants to increase the representation of European genomes, particularly human isolates, confirming A. phagocytophilum population structure patterns previously inferred from limited gene-based and provide new potential genomic markers that may help identify lineages associated with zoonotic transmission.