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The objectives:

Our group is interested in the interactions between vertebrate hosts and tick-borne pathogens, and in particular pathogenic bacteria vectored by ticks of the genus Ixodes.

HL-60 cell infected with A. phagocytophilum strain NY18 (human American) (UMR BIPAR©)

Our objectives are both cognitive and targeted, using multiple approaches (from the ecosystem to the cellular and molecular levels).

Our main objectives are as follows:

Cognitive level:

I- To explore the issue of species barriers and how they are crossed, particularly in the case of zoonotic agents.
II- To identify the determinants of the virulence of these pathogens
III- To study the mechanisms by which pathogens adapt to the alternation between vertebrate and invertebrate hosts
IV- To study the impact of tick microbiota on the transmission of these agents (alone or in the context of co-infection) to vertebrate hosts.
V- To explore the transmission cycles of these pathogens and identify reservoir hosts in wildlife

Targeted level:

I- To gain a better understanding of the epidemiological situation in the Ile-de-France region, particularly as regards the infection of wild fauna, especially synanthropic fauna, by vector-borne agents.
II- To develop tools for studying these pathogens in the laboratory
III- To develop means of screening/diagnosis, monitoring and control of these pathogens with an economic and/or zoonotic impact.

In recent years, the VAMP group has focused in particular on a strict intracellular bacterium, Anaplasma phagocytophilum, because of its impact, both economic (particularly for cattle: abortions, production losses, etc.) and zoonotic. The difficulties associated with isolating and cultivating this bacterium mean that it is still little-known, The difficulties associated with its isolation and cultivation make it a bacterium that is still little known and which confronts researchers and actors in the field with many challenges.

Bovine (left) and canine (right) neutrophils infected with A. phagocytophilum (UMR BIPAR©)

This work forms part of the MiTick team's other activities, with the aim of contributing to better control of emerging tick-associated infections.

Major results:

The results achieved in recent years, and which are currently being pursued, include the development of research tools, which are sorely lacking, in particular :

I- Development of tools for the molecular typing of A. phagocytophilum: an MLVA technique has been developed which has made it possible to study in greater detail the characteristics of bovine strains and to link them to a probable reservoir in Europe, the Elaphe Deer:

A new multiple-locus variable-number tandem repeat analysis reveals different clusters for Anaplasma phagocytophilum circulating in domestic and wild ruminants, 2014, Dugat et al. Parasit Vectors

Multiple-locus variable-number tandem repeat analysis potentially reveals the existence of two groups of Anaplasma phagocytophilum circulating in cattle in France with different wild reservoirs, 2016, Dugat et al. Parasit Vectors

II- Development of a sequence capture technique, which enabled us to sequence a bovine strain of A. phagocytophilum for the 1st time, with extension to the sequencing of animal strains circulating in France and Europe in an attempt to determine their phylogenetic links:

Comparative genomics of first available bovine Anaplasma phagocytophilum genome obtained with targeted sequence capture, 2014, Dugat et al., BMC Genomics

Draft Anaplasma phagocytophilum Genome Sequences from Five Cows, Two Horses, and One Roe Deer Collected in Europe, 2016, Dugat et al., Genome Announc.

III- Demonstration of the ability of a particular molecular type of A. phagocytophilum to circulate in vectors other than I. ricinus in regions of France where it is absent:

One particular Anaplasma phagocytophilum ecotype infects cattle in the Camargue, France, 2017, Dugat et al. Parasit Vectors

IV- Longitudinal study of the persistence of strains on farms: evidence of long-term infection of cattle and coinfection of cattle by several strains of A. phagocytophilum:

Co-circulation of different A. phagocytophilum variants within cattle herds and possible reservoir role for cattle, 2018, Lagrée et al. Parasit Vectors

V- Development of bovine endothelial cell lines to explore their permissiveness towards A. phagocytophilum and their potential role as niche cells:

Bovine Organospecific Microvascular Endothelial Cell Lines as New and Relevant In Vitro Models to Study Viral Infections, 2020, Lagrée et al., Int J Mol Sci.

Current projects:

The group is currently carrying out a number of projects relating to :

• Culture of A. phagocytophilum strains and study of their interactions with vertebrate host cells

HL-60 cells infected with strain NY18 observed under a x100 light microscope (UMR BIPAR©)

ISE6 cells infected with the NV2Os strain, observed with a x100 light microscope (UMR BIPAR©)

• The development of myeloid bovine cell lines, to provide cells for the culture of A. phagocytophilum strains from ruminants in vertebrate systems (in progress).
• Sequencing the DNA of A. phagocytophilum from humans and various vertebrate hosts in order to search for virulence factors and/or factors affecting the species barrier or its transgression (results currently being analysed).
• The development of aptamers, essential tools for further study of A. phagocytophilum and other vector-borne pathogens (PhD in progress)
• Exploring the infection of wildlife in the Ile-de-France region, in particular synanthropes (several veterinary theses in progress)
• Studying the impact of Midichloria (and other symbionts of the I. ricinus tick) on transmission by the A. phagocytophilum tick alone or in a co-infection system (Borrelia burgdorferisl or TBEV) (Labex project underway)

Collaborations:

• Aptamers: Frédéric Ducongé (CEA, CNRS UMR 9199, Université Paris-Saclay, MIRCen, Fontenay-aux-Roses), Gunter Mayer (LIMES Institute, University of Bonn, Germany)
• Sequencing of strains: Benoît Jaulhac (CNR Borrelia, CHU de Strasbourg), Virginie Chesnais (SPAAD, ANSES, Maisons-Alfort), Claude Saegerman (Faculty of Veterinary Medicine, University of Liège), OSCAR network (Observatoire et suivi des causes d'avortement bovins) (GDS France)
• Symbiotes and co-infections: Olivier Plantard (BIOEPAR, INRAE, Nantes)
• Study of synanthropic and non-synanthropic wild fauna: Pascal Arné and Cécile le Barzic (Chuv-FS, EnvA, Maisons-Alfort), Nora Madani (UZB, ANSES, Maisons-Alfort), Zorée Djelouadji (RS2GP Unit, VetAgroSup, Marcy-l'Etoile), Maud Marsot (LSAN, ANSES, Maisons-Alfort)
• Development of bovine cell lines: Yves Milleman and Bérangère Ravary (Chuv-AP, EnvA, Maisons-Alfort), Laurence Guyonneau-Harmand and Quentin Brunet-Manquat (EFS, Hopital Saint-Louis, Paris), Catherine Grillon (CBM, CNRS, Orléans)