Diversité génomique des bactéries pathogènes du complexe d’espèces Borrelia burgdorferi : évolution et épidémiologie moléculaire

Infectious diseases are one of the major causes of human and animal morbidity, and they have impacts on the economy, public health, and the environment. By studying the diversity of the pathogens responsible for these diseases and their circulation within host communities and among vectors, we may glean valuable information that will aid prevention and control efforts. For these reasons, during my thesis, I became particularly interested in the pathogen(s) responsible for Lyme disease. This disease is caused by bacteria belonging to the Borrelia burgdorferi sensu lato (s.l.) species complex that are transmitted by ticks (during their blood meals) and that can infect several vertebrate host species. When I analyzed the genetic diversity present in 63 B. burgdorferi s.l. strains, whose genomes had been sequenced, I found that there was a significant degree of genetic separation among the different genospecies making up the complex. My results suggest that the fact that these different bacterial groups infect different ranges of hosts B. burgdorferi s.s. is mainly a pathogen of small mammals and B. garinii is primarily associated with birds lead to distinct population dynamics. Moreover, thanks to the high-throughput sequencing of two genetic markers, I have been able to show that, at an intraspecific level, certain B. burgdorferi genotypes are associated with specific rodent species. Finally, using the pathogen diversity observed in rodents and ticks, I employed a modeling approach to estimate the human disease risks presented by an introduced host species (the Siberian chipmunk) and found that these risks could be significant.Les maladies infectieuses sont une des causes les plus importantes de morbidité chez l'homme et l'animal avec des conséquences à la fois économiques, sanitaires et écologiques. L'étude de la diversité des pathogènes responsables et de leurs dynamiques de circulation au sein des communautés d'hôtes et de vecteurs, peut fournir des informations importantes pour la prévention et le contrôle de ces maladies. Dans ce contexte, nous nous sommes intéressés à l'agent pathogène responsable de la maladie de Lyme. Cette maladie est causée par les bactéries du complexe d'espèces Borrelia burgdorferi sensu lato (s.l.) transmises par les tiques lors de repas sanguins et sont capables d'infecter plusieurs espèces d'hôtes vertébrés. L'analyse de la diversité génétique de 63 souches de B. burgdorferi s.l., dont les génomes ont été séquencés, ont révélé un degré d'isolement génétique très important entre les différentes espèces du complexe. Les résultats obtenus suggèrent que les différents spectres d'hôtes des lignées de B. burgdorferi s.s. (principalement associées aux petits mammifères) et de B. garinii (normalement associées aux oiseaux) conduisent à des dynamiques de populations distinctes. De plus, grâce au séquençage haut-débit de deux marqueurs, nous avons pu démontrer qu'il existe, à une échelle intra-spécifique, des associations préférentielles des génotypes de B. burgdorferi avec différentes espèces de rongeurs. Enfin, en utilisant la diversité observée chez ces rongeurs et celle chez les tiques, nous avons estimé, via une approche de modélisation, que la contribution au risque de la maladie pour l'homme d'une espèce hôte introduite (tamia de Sibérie), pouvait être importante

Bluetongue virus spread in Europe is a consequence of climatic, landscape and vertebrate host factors as revealed by phylogeographic inference

Spatio-temporal patterns of the spread of infectious diseases are commonly driven by environmental and ecological factors. This is particularly true for vector-borne diseases because vector populations can be strongly affected by host distribution as well as by climatic and landscape variables. Here, we aim to identify environmental drivers for bluetongue virus (BTV), the causative agent of a major vector-borne disease of ruminants that has emerged multiple times in Europe in recent decades. In order to determine the importance of climatic, landscape and host-related factors affecting BTV diffusion across Europe, we fitted different phylogeographic models to a dataset of 113 time-stamped and geo-referenced BTV genomes, representing multiple strains and serotypes. Diffusion models using continuous space revealed that terrestrial habitat below 300 m altitude, wind direction and higher livestock densities were associated with faster BTV movement. Results of discrete phylogeographic analysis involving generalized linear models broadly supported these findings, but varied considerably with the level of spatial partitioning. Contrary to common perception, we found no evidence for average temperature having a positive effect on BTV diffusion, though both methodological and biological reasons could be responsible for this result. Our study provides important insights into the drivers of BTV transmission at the landscape scale that could inform predictive models of viral spread and have implications for designing control strategies

Genomic Diversity of the Ostreid Herpesvirus Type 1 Across Time and Location and Among Host Species

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. This is particularly true for pathogens with low per-site mutation rates, such as DNA viruses, that do not exhibit a large amount of evolutionary change among genetic sequences sampled at different time points. However, whole-genome sequencing can reveal the accumulation of novel genetic variation between samples, promising to render most, if not all, microbial pathogens measurably evolving and suitable for analytical techniques derived from population genetic theory. Here, we aim to assess the measurability of evolution on epidemiological time scales of the Ostreid herpesvirus 1 (OsHV-1), a double stranded DNA virus of which a new variant, OsHV-1 μVar, emerged in France in 2008, spreading across Europe and causing dramatic economic and ecological damage. We performed phylogenetic analyses of heterochronous (n = 21) OsHV-1 genomes sampled worldwide. Results show sufficient temporal signal in the viral sequences to proceed with phylogenetic molecular clock analyses and they indicate that the genetic diversity seen in these OsHV-1 isolates has arisen within the past three decades. OsHV-1 samples from France and New Zealand did not cluster together suggesting a spatial structuration of the viral populations. The genome-wide study of simple and complex polymorphisms shows that specific genomic regions are deleted in several isolates or accumulate a high number of substitutions. These contrasting and non-random patterns of polymorphism suggest that some genomic regions are affected by strong selective pressures. Interestingly, we also found variant genotypes within all infected individuals. Altogether, these results provide baseline evidence that whole genome sequencing could be used to study population dynamic processes of OsHV-1, and more broadly herpesviruses

Genomic diversity of pathogenic bacteria in the Borrelia burgdorferi species complex : evolution and molecular epidemiology

Les maladies infectieuses sont une des causes les plus importantes de morbidité chez l'homme et l'animal avec des conséquences à la fois économiques, sanitaires et écologiques. L'étude de la diversité des pathogènes responsables et de leurs dynamiques de circulation au sein des communautés d'hôtes et de vecteurs, peut fournir des informations importantes pour la prévention et le contrôle de ces maladies. Dans ce contexte, nous nous sommes intéressés à l'agent pathogène responsable de la maladie de Lyme. Cette maladie est causée par les bactéries du complexe d'espèces Borrelia burgdorferi sensu lato (s.l.) transmises par les tiques lors de repas sanguins et sont capables d'infecter plusieurs espèces d'hôtes vertébrés. L'analyse de la diversité génétique de 63 souches de B. burgdorferi s.l., dont les génomes ont été séquencés, ont révélé un degré d'isolement génétique très important entre les différentes espèces du complexe. Les résultats obtenus suggèrent que les différents spectres d'hôtes des lignées de B. burgdorferi s.s. (principalement associées aux petits mammifères) et de B. garinii (normalement associées aux oiseaux) conduisent à des dynamiques de populations distinctes. De plus, grâce au séquençage haut-débit de deux marqueurs, nous avons pu démontrer qu'il existe, à une échelle intra-spécifique, des associations préférentielles des génotypes de B. burgdorferi avec différentes espèces de rongeurs. Enfin, en utilisant la diversité observée chez ces rongeurs et celle chez les tiques, nous avons estimé, via une approche de modélisation, que la contribution au risque de la maladie pour l'homme d'une espèce hôte introduite (tamia de Sibérie), pouvait être importante.Infectious diseases are one of the major causes of human and animal morbidity, and they have impacts on the economy, public health, and the environment. By studying the diversity of the pathogens responsible for these diseases and their circulation within host communities and among vectors, we may glean valuable information that will aid prevention and control efforts. For these reasons, during my thesis, I became particularly interested in the pathogen(s) responsible for Lyme disease. This disease is caused by bacteria belonging to the Borrelia burgdorferi sensu lato (s.l.) species complex that are transmitted by ticks (during their blood meals) and that can infect several vertebrate host species. When I analyzed the genetic diversity present in 63 B. burgdorferi s.l. strains, whose genomes had been sequenced, I found that there was a significant degree of genetic separation among the different genospecies making up the complex. My results suggest that the fact that these different bacterial groups infect different ranges of hosts B. burgdorferi s.s. is mainly a pathogen of small mammals and B. garinii is primarily associated with birds lead to distinct population dynamics. Moreover, thanks to the high-throughput sequencing of two genetic markers, I have been able to show that, at an intraspecific level, certain B. burgdorferi genotypes are associated with specific rodent species. Finally, using the pathogen diversity observed in rodents and ticks, I employed a modeling approach to estimate the human disease risks presented by an introduced host species (the Siberian chipmunk) and found that these risks could be significant

Multiple independent transmission cycles of a tick-borne pathogen within a local host community

Many pathogens are maintained by multiple host species and involve multiple strains with potentially different phenotypic characteristics. Disentangling transmission patterns in such systems is often challenging, yet investigating how different host species contribute to transmission is crucial to properly assess and manage disease risk. We aim to reveal transmission cycles of bacteria within the Borrelia burgdorferi species complex, which include Lyme disease agents. We characterized Borrelia genotypes found in 488 infected Ixodes ricinus nymphs collected in the Sénart Forest located near Paris (France). These genotypes were compared to those observed in three sympatric species of small mammals and network analyses reveal four independent transmission cycles. Statistical modelling shows that two cycles involving chipmunks, an introduced species, and non-sampled host species such as birds, are responsible for the majority of tick infections. In contrast, the cycle involving native bank voles only accounts for a small proportion of infected ticks. Genotypes associated with the two primary transmission cycles were isolated from Lyme disease patients, confirming the epidemiological threat posed by these strains. Our work demonstrates that combining high-throughput sequence typing with networks tools and statistical modeling is a promising approach for characterizing transmission cycles of multi-host pathogens in complex ecological settings

Geographic range overlap rather than phylogenetic distance explains rabies virus transmission among closely related bat species

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Influence de la météorologie sur la dynamique des populations des stades libres des tiques<em> Ixodes ricinus</em> et <em>i. Frontalis</em> : determination des fenetres temporelles optimales par l’approche des cross correlation maps

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Influence de la météorologie sur la dynamique des populations des stades libres des tiques<em> Ixodes ricinus</em> et <em>i. Frontalis</em> : determination des fenetres temporelles optimales par l’approche des cross correlation maps

National audienc