Exploration of geographical population structure of Anaplasma phagocytophilum: Insights from 12 newly sequenced European human and bovine genome assemblies. - 2026
Exploration of geographical population structure of Anaplasma phagocytophilum: Insights from 12 newly sequenced European human and bovine genome assemblies.
Rouxel, Clotilde; Deshuillers, Pierre Lucien; Vila-Nova, Merylet al.
2026 • In Current research in parasitology and vector-borne diseases, 9, p. 100393
[en] 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Rouxel, Clotilde ; ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort (EnvA), Laboratoire de Santé Animale, BIPAR, Maisons-Alfort, F-94700, France
Deshuillers, Pierre Lucien ; ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort (EnvA), Laboratoire de Santé Animale, BIPAR, Maisons-Alfort, F-94700, France
Vila-Nova, Meryl; ANSES, Laboratoire de Sécurité Alimentaire, Laboratoire de Santé Animale, SPAAD, Maisons-Alfort, F-94700, France
Merda, Deborah; ANSES, Laboratoire de Sécurité Alimentaire, Laboratoire de Santé Animale, SPAAD, Maisons-Alfort, F-94700, France
Boyer, Pierre; Université de Strasbourg, UR3073 PHAVI, CHRU de Strasbourg, Instituts de Bactériologie et de Parasitologie, 3, rue Koeberlé, Strasbourg, F-67000, France ; CNR des Borrelia, Hôpitaux Universitaires de Strasbourg, Strasbourg, F-67000, France
Jaulhac, Benoit; Université de Strasbourg, UR3073 PHAVI, CHRU de Strasbourg, Instituts de Bactériologie et de Parasitologie, 3, rue Koeberlé, Strasbourg, F-67000, France ; CNR des Borrelia, Hôpitaux Universitaires de Strasbourg, Strasbourg, F-67000, France
Saegerman, Claude ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Epidémiologie, analyse de risques et biosécurité appliquées aux sciences vétérinaires
Delooz, Laurent ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) ; Regional Association for Animal Registration and Health (ARSIA) asbl, Ciney, 5590, Belgium
Kuntz, Grégoire; Innoval, GDS Bretagne, Ploufragan, 22 440, France
Boulouis, Henri-Jean; ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort (EnvA), Laboratoire de Santé Animale, BIPAR, Maisons-Alfort, F-94700, France
Haddad, Nadia; ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort (EnvA), Laboratoire de Santé Animale, BIPAR, Maisons-Alfort, F-94700, France
Lagrée, Anne-Claire ; ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort (EnvA), Laboratoire de Santé Animale, BIPAR, Maisons-Alfort, F-94700, France
Chesnais, Virginie ; ANSES, Laboratoire de Sécurité Alimentaire, Laboratoire de Santé Animale, SPAAD, Maisons-Alfort, F-94700, France
Exploration of geographical population structure of Anaplasma phagocytophilum: Insights from 12 newly sequenced European human and bovine genome assemblies.
Publication date :
2026
Journal title :
Current research in parasitology and vector-borne diseases
This work was supported by the French Government's Investment for the Future program as a Laboratory of Excellence in \u201CIntegrative Biology of Emerging Infectious Diseases\u201D (grant No. ANR-10-LABEX-62-IBEID). The Animal Health Department of INRAe supported specifically the sequencing of bovine samples.This work was supported by the French Government\u2019s Investment for the Future program as a Laboratory of Excellence in \u201C Integrative Biology of Emerging Infectious Diseases \u201D (grant No. ANR-10-LABEX-62-IBEID ). The Animal Health Department of INRAe supported specifically the sequencing of bovine samples.
Al-Khedery, B., Barbet, A., Comparative genomics identifies a potential marker of human-virulent Anaplasma phagocytophilum. Pathogens 3 (2014), 25–35, 10.3390/pathogens3010025.
Azagi, T., Dirks, R.P., Yebra-Pimentel, E.S., Schaap, P.J., Koehorst, J.J., Esser, H.J., Sprong, H., Assembly and comparison of Ca. Neoehrlichia mikurensis genomes. Microorganisms, 10, 2022, 1134, 10.3390/microorganisms10061134.
Azagi, T., Hoornstra, D., Kremer, K., Hovius, J.W.R., Sprong, H., Evaluation of disease causality of rare Ixodes ricinus-borne infections in Europe. Pathogens, 9, 2020, 150, 10.3390/pathogens9020150.
Barbet, A.F., Al-Khedery, B., Stuen, S., Granquist, E.G., Felsheim, R.F., Munderloh, U.G., An emerging tick-borne disease of humans is caused by a subset of strains with conserved genome structure. Pathogens, 10, 2013, 544, 10.3390/pathogens2030544.
Courtney, J.W., Kostelnik, L.M., Zeidner, N.S., Massung, R.F., Multiplex real-time PCR for detection of Anaplasma phagocytophilum and Borrelia burgdorferi. J. Clin. Microbiol. 42 (2004), 3164–3168, 10.1128/JCM.42.7.3164-3168.2004.
Crosby, F.L., Eskeland, S., Bø-Granquist, E.G., Munderloh, U.G., Price, L.D., Al-Khedery, B., et al. Comparative whole genome analysis of an Anaplasma phagocytophilum strain isolated from Norwegian sheep. Pathogens, 11, 2022, 601, 10.3390/pathogens11050601.
Delooz, L., Czaplicki, G., Houtain, J.Y., Dal Pozzo, F., Saegerman, C., Laboratory findings suggesting an association between BoHV-4 and bovine abortions in southern Belgium. Transbound. Emerg. Dis. 64 (2017), 1100–1109.
Didelot, X., Wilson, D.J., ClonalFrameML: efficient inference of recombination in whole bacterial genomes. PLoS Comput. Biol., 11, 2015, e1004041, 10.1371/journal.pcbi.1004041.
Dixon, D.M., Branda, J.A., Clark, S.H., Dumler, J.S., Horowitz, H.W., Perdue, S.S., et al. Ehrlichiosis and anaplasmosis subcommittee report to the tick-borne disease working group. Ticks Tick Borne Dis., 12, 2021, 101823, 10.1016/j.ttbdis.2021.101823.
Dugat, T., Lagrée, A.-C., Maillard, R., Boulouis, H., Haddad, N., Opening the black box of Anaplasma phagocytophilum diversity: current situation and future perspectives. Front. Cell. Infect. Microbiol., 5, 2015, 61, 10.3389/fcimb.2015.00061.
Dugat, T., Loux, V., Marthey, S., Moroldo, M., Lagrée, A.-C., Boulouis, H.-J., et al. Comparative genomics of first available bovine Anaplasma phagocytophilum genome obtained with targeted sequence capture. BMC Genom., 15, 2014, 973.
Dugat, T., Rossignol, M.-N., Rué, O., Loux, V., Marthey, S., Moroldo, M., et al. Draft Anaplasma phagocytophilum genome sequences from five cows, two horses, and one roe deer collected in Europe. Genome Announc., 4, 2016, e00950, 10.1128/genomeA.00950-16 16.
Dumler, J.S., Barbet, A.F., Bekker, C.P., Dasch, G.A., Palmer, G.H., Ray, S.C., et al. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and “HGE agent” as subjective synonyms of Ehrlichia phagocytophila. Int. J. Syst. Evol. Microbiol. 51 (2001), 2145–2165, 10.1099/00207713-51-6-2145.
Dumler, J.S., Choi, K.-S., Garcia-Garcia, J.C., Barat, N.S., Scorpio, D.G., Garyu, J.W., et al. Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerg. Infect. Dis. 11 (2005), 1828–1834.
Gautreau, G., Bazin, A., Gachet, M., Planel, R., Burlot, L., Dubois, M., et al. PPanGGOLiN: depicting microbial diversity via a partitioned pangenome graph. PLoS Comput. Biol., 16, 2020, e1007732, 10.1371/journal.pcbi.1007732.
Jaarsma, R.I., Sprong, H., Takumi, K., Kazimirova, M., Silaghi, C., Mysterud, A., et al. Anaplasma phagocytophilum evolves in geographical and biotic niches of vertebrates and ticks. Parasites Vectors, 12, 2019, 328, 10.1186/s13071-019-3583-8.
Jahfari, S., Coipan, E.C., Fonville, M., van Leeuwen, A.D., Hengeveld, P., Heylen, D., et al. Circulation of four Anaplasma phagocytophilum ecotypes in Europe. Parasites Vectors, 7, 2014, 365, 10.1186/1756-3305-7-365.
Jain, C., Rodriguez-R, L.M., Phillippy, A.M., Konstantinidis, K.T., Aluru, S., High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat. Commun., 9, 2018, 5114, 10.1038/s41467-018-07641-9.
Jin, H., Wei, F., Liu, Q., Qian, J., Epidemiology and control of human granulocytic anaplasmosis: a systematic review. Vector Borne Zoonotic Dis. 12 (2012), 269–274, 10.1089/vbz.2011.0753.
Koebel, C., Kern, A., Edouard, S., Hoang, A.T., Celestin, N., Hansmann, Y., et al. Human granulocytic anaplasmosis in eastern France: clinical presentation and laboratory diagnosis. Diagn. Microbiol. Infect. Dis. 72 (2012), 214–218, 10.1016/j.diagmicrobio.2011.12.005.
Langenwalder, D.B., Schmidt, S., Silaghi, C., Skuballa, J., Pantchev, N., Matei, I.A., et al. The absence of the drhm gene is not a marker for human-pathogenicity in European Anaplasma phagocytophilum strains. Parasites Vectors, 13, 2020, 238, 10.1186/s13071-020-04116-z.
Lees, J.A., Galardini, M., Bentley, S.D., Weiser, J.N., Corander, J., pyseer: a comprehensive tool for microbial pangenome-wide association studies. Bioinformatics 34 (2018), 4310–4312, 10.1093/bioinformatics/bty539.
Lesiczka, P.M., von Loewenich, F.D., Kohl, R., Krawczyk, A.I., Dirks, R.P., Boyer, P.H., et al. European human granulocytic anaplasmosis is caused by a subcluster of Anaplasma phagocytophilum Ecotype I. Curr. Res. Parasitol. Vector-Borne Dis., 8, 2025, 100324, 10.1016/j.crpvbd.2025.100324.
Li, H., New strategies to improve minimap2 alignment accuracy. Bioinformatics 37 (2021), 4572–4574, 10.1093/bioinformatics/btab705.
Matei, I.A., Estrada-Peña, A., Cutler, S.J., Vayssier-Taussat, M., Varela-Castro, L., Potkonjak, A., et al. A review on the eco-epidemiology and clinical management of human granulocytic anaplasmosis and its agent in Europe. Parasites Vectors, 12, 2019, 599, 10.1186/s13071-019-3852-6.
Neave, M.J., Mileto, P., Joseph, A., Reid, T.J., Scott, A., Williams, D.T., Keyburn, A.L., Comparative genomic analysis of the first Ehrlichia canis detections in Australia. Ticks Tick Borne Dis., 13, 2022, 101909, 10.1016/j.ttbdis.2022.101909.
Ondov, B.D., Starrett, G.J., Sappington, A., Kostic, A., Koren, S., Buck, C.B., Phillippy, A.M., Mash Screen: high-throughput sequence containment estimation for genome discovery. Genome Biol., 20, 2019, 232, 10.1186/s13059-019-1841-x.
Pritchard, L., Glover, R.H., Humphris, S., Elphinstone, J.G., Toth, I.K., Genomics and taxonomy in diagnostics for food fecurity: foft-rotting enterobacterial plant pathogens. Anal. Methods 8 (2015), 12–24, 10.1039/C5AY02550H.
Wright, S., The interpretation of population structure by F-statistics with special regard to systems of mating. Evolution 19 (1965), 395–420, 10.1111/j.1558-5646.1965.tb01731.