Comparative Whole Genome Analysis of an Anaplasma phagocytophilum Strain Isolated from Norwegian Sheep

Francy L. Crosby, Sveinung Eskeland, Erik G. Bø-Granquist, Ulrike G. Munderloh, Lisa D. Price, Basima Al-Khedery, Snorre Stuen, Anthony F. Barbet

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Anaplasma phagocytophilum is a Gram-negative obligate intracellular tick-borne alphapro-teobacteria (family Anaplasmatacea, order Rickettsiales) with a worldwide distribution. In Norway, tick borne fever (TBF), caused by A. phagocytophilum, presents a major challenge in sheep farming. Despite the abundance of its tick vector, Ixodes ricinus, and A. phagocytophilum infections in wild and domestic animals, reports of infections in humans are low compared with cases in the U.S. Although A. phagocytophilum is genetically diverse and complex infections (co-infection and superinfection) in ruminants and other animals are common, the underlying genetic basis of intra-species interactions and host-specificity remains unexplored. Here, we performed whole genome comparative analysis of a newly cultured Norwegian A. phagocytophilum isolate from sheep (ApSheep_NorV1) with 27 other A. phagocytophilum genome sequences derived from human and animal infections worldwide. Although the compared strains are syntenic, there is remarkable genetic diversity between different genomic loci including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen Msp2/p44. Blast comparisons between the msp2/p44 pseudogene repertoires from all the strains showed high divergence between U. S. and European strains and even between two Norwegian strains. Based on these comparisons, we concluded that in ruminants, complex infections can be attributed to infection with strains that differ in their msp2/p44 repertoires, which has impor-tant implications for pathogen evolution and vaccine development. We also present evidence for integration of rickettsial DNA into the genome of ISE6 tick cells.

Original languageEnglish (US)
Article number601
Issue number5
StatePublished - May 2022

Bibliographical note

Funding Information:
Funding: This work was supported by the Norwegian research funding for agriculture and the food industry (Matfondavtalen) grant number: 244173/E50, the Norwegian Meat and Poultry Research Centre, and the Norwegian Association of Sheep and Goat Farmers (NSG). The funding body had no role in the study design, collection, analysis, interpretation of data, and in writing the manuscript.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Anaplasma phagocytophilum
  • co-infection
  • comparative genomics
  • lateral gene transfer
  • tick-borne fever
  • ticks


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