The absence of the drhm gene is not a marker for human‑pathogenicity in European Anaplasma phagocytophilum strains
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Abstract
Background: Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil
granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness in humans and
animals. The geographical distribution of A. phagocytophilum spans the Americas, Europe, Africa and Asia. However,
human disease predominantly occurs in North America but is infrequently reported from Europe and Asia. In North
American strains, the absence of the drhm gene has been proposed as marker for pathogenicity in humans whereas
no information on the presence or absence of the drhm gene was available for A. phagocytophilum strains circulating
in Europe. Therefore, we tested 511 European and 21 North American strains for the presence of drhm and compared
the results to two other typing methods: multilocus sequence typing (MLST) and ankA-based typing.
Results: Altogether, 99% (478/484) of the analyzable European and 19% (4/21) of the North American samples from
different hosts were drhm-positive. Regarding the strains from human granulocytic anaplasmosis cases, 100% (35/35)
of European origin were drhm-positive and 100% (14/14) of North American origin were drhm-negative. Human
strains from North America and Europe were both part of MLST cluster 1. North American strains from humans
belonged to ankA gene clusters 11 and 12 whereas European strains from humans were found in ankA gene cluster
1. However, the North American ankA gene clusters 11 and 12 were highly identical at the nucleotide level to the
European cluster 1 with 97.4% and 95.2% of identity, respectively.
Conclusions: The absence of the drhm gene in A. phagocytophilum does not seem to be associated with pathogenicity
for humans per se, because all 35 European strains of human origin were drhm-positive. The epidemiological
differences between North America and Europe concerning the incidence of human A. phagocytophilum infection are
not explained by strain divergence based on MLST and ankA gene-based typing.
Keywords: Anaplasma phagocytophilum, ankA, APH_0919, APH_0922, Asia, drhm, Europe, Human, Multilocus
sequence typing (MLST), North America, Pathogenicity