The absence of the drhm gene is not a marker for human-pathogenicity in European Anaplasma phagocytophilum strains

Denis B Langenwalder,Ioana A Matei,Urs Gilli,Sabine Schmidt,Miroslav Petrovec,Martin Ganter,Friederike D Von Loewenich,Erik Salaneck,Nikola Pantchev,Cornelia Silaghi,Jasmin Skuballa,Joanna Zajkowska,Tove Hoffman,Andrei D Mihalca

doi:10.1186/s13071-020-04116-z

Abstract

BackgroundAnaplasma 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.ResultsAltogether, 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.ConclusionsThe 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.

Highlights

IntroductionHuman disease predominantly occurs in North America but is infrequently reported from Europe and Asia
Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes
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

Summary

Introduction

Human disease predominantly occurs in North America but is infrequently reported from Europe and Asia. Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes [1]. It causes febrile illness in humans and animals and is transmitted by ticks of the Ixodes ricinus complex [2, 3]. Most patients from China initially described as to be infected by A. phagocytophilum suffered from a bunyavirus infection called severe fever with thrombocytopenia syndrome (SFTS) [5, 10,11,12]

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