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Evolution and adaptation of tickborne pathogens across Eurasia
Evolution and adaptation of tickborne pathogens across Eurasia
Ticks are obligate, blood feeding parasites of vertebrate animals and further act as vectors for many vector-borne pathogens including some causing human and animal disease. One such pathogen is Borrelia burgdorferi sensu lato (Bbsl), which describes a diverse species complex of spirochete bacteria that exist in an obligate transmission cycle between ixodid ticks and various vertebrate reservoir hosts. Some of these Bbsl genospecies are of epidemiological concern as they are the causative agents of human Lyme borreliosis (LB); the most common vector-borne disease in the Northern hemisphere. Due to their ecology, these genospecies undergo complex evolutionary and selective pressures driving adaptation to new host and vector species, but also maintain a high level of within-species diversity. These processes are thought to further drive speciation events and expansion of Bbsl genospecies into new geographic ranges. Evolutionary studies are currently impeded by a lack of isolates and associated genomic data including populations, such as those in Asia, having been neglected in the past. Combining ecological and genomic data, would open the way to studying the genetic underpinnings of both host and vector adaptation, variability in the severity of human LB, and how these bacteria may adapt to changing environments. The Eurasian Bbsl system offers a unique opportunity to utilize this evolutionary ecology approach to study Bbsl evolution. Currently three LB-causing Bbsl genospecies (Borrelia afzelii, Borrelia bavariensis, Borrelia garinii) share a Eurasian distribution and are transmitted by different generalist tick vectors: Ixodes ricinus (Europe) or Ixodes persulcatus (Asia). These genospecies further differ in their host associations and human LB manifestations, making them prime candidates for comparative genomics studies to understand the genetic underpinnings of these factors. The main aim of this dissertation was to study Bbsl from an evolutionary ecology approach and to produce isolates of pathogenic, Eurasian Bbsl genospecies with associated genomic data to fill current gaps in our knowledge of these genospecies. We utilized ecological (Papers 1-3), genomic (Papers 4-5), and molecular based (Paper 6) studies to answer questions related to the evolution of these genospecies. In Paper 1, we screened migratory birds transiting through the Italian island of Ponza for exotic tick species and tick-borne pathogens, including bacteria and viruses. Through this we were able to confirm the role of migratory birds in the movement of exotic ticks and associated pathogens into new geographic areas. We then collected Ixodes ricinus ticks longitudinally over a 10-year period in Latvia (Paper 2) and in a single year (2019) in multiple plots in southern-Germany (Paper 3). These studies allowed us to hypothesize that both along spatial and temporal scales that Bbsl diversity and prevalence is influenced predominantly by host community structure, leading to both highly stable and dynamic Bbsl communities. Utilizing then existing genomic data and recently sequenced Russian isolates of B. bavariensis, we characterized the full genomes of 33 isolates in Paper 4. This allowed us to see that, even in the almost clonal European population, we observe a high level of within-species diversity including novel findings such as higher plasmid copy number than expected from previous literature. From this we further characterized the evolutionary history of 142 isolates belonging to B. afzelii, B. bavariensis, and B. garinii based on assembled chromosomes corrected for recombining regions. Through this we were able to support that all three genospecies share an Asian origin (already shown for B. bavariensis in Paper 4 and previous work) and that colonization of Europe resulted through adaptation to a novel tick vector (I. ricinus). This also was paired with the fact that post-colonization gene flow for the different genospecies appeared to correlate with the mobility of proposed reservoir hosts. This allowed us to make testable hypotheses regarding the evolution and ecology of these three genospecies. Both Paper 4 and 5, characterized a high level of within-species diversity even in our samples which we hypothesize could influence Bbsl spirochete interactions with both host and vector species. Paper 6 characterizes one instance of within-species variation where two European B. bavariensis isolates (PBN and PNi) were found to naturally lack the entire PFam54 gene array. This gene array is known to encode protein products important for evading the host’s innate immune system, cell adhesion, and survival in the tick midgut. Their natural absence did increases susceptibility to human complement, an important pillar of innate immunity. Even so, these isolates remained infectious to mice post intradermal inoculation but did differ in how efficiently they can colonize certain mouse tissues. This highlighted that these genes are not required for mouse infectivity but potentially play a larger role in human pathogenicity. There is just one instance of within-species variability and is related to gene loss instead of sequence variation. Our results show that a high level of diversity does exist across the Eurasian range of these three genospecies which requires further research to understand how variability relates to the evolution of human pathogenicity, vector adaptation, and host adaptation. Taken together, our results allowed us to better understand how these genospecies evolved across their geographic range. We were able to integrate ecological and genomics-based studies to show that geographic expansion appears to relate to vector adaptation while divergence, and potentially speciation, appears to be driven by host-adaptation. Utilizing an evolutionary ecology perspective, we were able to also identify unexpected results, such as the lack of geographic structure in the Asian B. bavariensis isolates, and through this create testable hypotheses regarding Bbsl ecology. Our analysis further was able to show that natural within-species variation can influence transmission cycles and produced an isolate library (especially for Asian populations of LB-causing genospecies) which can be utilized in future lab-based transmission studies to determine how further variability can lead to adaptation or human pathogenicity in these bacteria.
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Rollins, Robert Ethan
2021
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Rollins, Robert Ethan (2021): Evolution and adaptation of tickborne pathogens across Eurasia. Dissertation, LMU München: Faculty of Biology
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Abstract

Ticks are obligate, blood feeding parasites of vertebrate animals and further act as vectors for many vector-borne pathogens including some causing human and animal disease. One such pathogen is Borrelia burgdorferi sensu lato (Bbsl), which describes a diverse species complex of spirochete bacteria that exist in an obligate transmission cycle between ixodid ticks and various vertebrate reservoir hosts. Some of these Bbsl genospecies are of epidemiological concern as they are the causative agents of human Lyme borreliosis (LB); the most common vector-borne disease in the Northern hemisphere. Due to their ecology, these genospecies undergo complex evolutionary and selective pressures driving adaptation to new host and vector species, but also maintain a high level of within-species diversity. These processes are thought to further drive speciation events and expansion of Bbsl genospecies into new geographic ranges. Evolutionary studies are currently impeded by a lack of isolates and associated genomic data including populations, such as those in Asia, having been neglected in the past. Combining ecological and genomic data, would open the way to studying the genetic underpinnings of both host and vector adaptation, variability in the severity of human LB, and how these bacteria may adapt to changing environments. The Eurasian Bbsl system offers a unique opportunity to utilize this evolutionary ecology approach to study Bbsl evolution. Currently three LB-causing Bbsl genospecies (Borrelia afzelii, Borrelia bavariensis, Borrelia garinii) share a Eurasian distribution and are transmitted by different generalist tick vectors: Ixodes ricinus (Europe) or Ixodes persulcatus (Asia). These genospecies further differ in their host associations and human LB manifestations, making them prime candidates for comparative genomics studies to understand the genetic underpinnings of these factors. The main aim of this dissertation was to study Bbsl from an evolutionary ecology approach and to produce isolates of pathogenic, Eurasian Bbsl genospecies with associated genomic data to fill current gaps in our knowledge of these genospecies. We utilized ecological (Papers 1-3), genomic (Papers 4-5), and molecular based (Paper 6) studies to answer questions related to the evolution of these genospecies. In Paper 1, we screened migratory birds transiting through the Italian island of Ponza for exotic tick species and tick-borne pathogens, including bacteria and viruses. Through this we were able to confirm the role of migratory birds in the movement of exotic ticks and associated pathogens into new geographic areas. We then collected Ixodes ricinus ticks longitudinally over a 10-year period in Latvia (Paper 2) and in a single year (2019) in multiple plots in southern-Germany (Paper 3). These studies allowed us to hypothesize that both along spatial and temporal scales that Bbsl diversity and prevalence is influenced predominantly by host community structure, leading to both highly stable and dynamic Bbsl communities. Utilizing then existing genomic data and recently sequenced Russian isolates of B. bavariensis, we characterized the full genomes of 33 isolates in Paper 4. This allowed us to see that, even in the almost clonal European population, we observe a high level of within-species diversity including novel findings such as higher plasmid copy number than expected from previous literature. From this we further characterized the evolutionary history of 142 isolates belonging to B. afzelii, B. bavariensis, and B. garinii based on assembled chromosomes corrected for recombining regions. Through this we were able to support that all three genospecies share an Asian origin (already shown for B. bavariensis in Paper 4 and previous work) and that colonization of Europe resulted through adaptation to a novel tick vector (I. ricinus). This also was paired with the fact that post-colonization gene flow for the different genospecies appeared to correlate with the mobility of proposed reservoir hosts. This allowed us to make testable hypotheses regarding the evolution and ecology of these three genospecies. Both Paper 4 and 5, characterized a high level of within-species diversity even in our samples which we hypothesize could influence Bbsl spirochete interactions with both host and vector species. Paper 6 characterizes one instance of within-species variation where two European B. bavariensis isolates (PBN and PNi) were found to naturally lack the entire PFam54 gene array. This gene array is known to encode protein products important for evading the host’s innate immune system, cell adhesion, and survival in the tick midgut. Their natural absence did increases susceptibility to human complement, an important pillar of innate immunity. Even so, these isolates remained infectious to mice post intradermal inoculation but did differ in how efficiently they can colonize certain mouse tissues. This highlighted that these genes are not required for mouse infectivity but potentially play a larger role in human pathogenicity. There is just one instance of within-species variability and is related to gene loss instead of sequence variation. Our results show that a high level of diversity does exist across the Eurasian range of these three genospecies which requires further research to understand how variability relates to the evolution of human pathogenicity, vector adaptation, and host adaptation. Taken together, our results allowed us to better understand how these genospecies evolved across their geographic range. We were able to integrate ecological and genomics-based studies to show that geographic expansion appears to relate to vector adaptation while divergence, and potentially speciation, appears to be driven by host-adaptation. Utilizing an evolutionary ecology perspective, we were able to also identify unexpected results, such as the lack of geographic structure in the Asian B. bavariensis isolates, and through this create testable hypotheses regarding Bbsl ecology. Our analysis further was able to show that natural within-species variation can influence transmission cycles and produced an isolate library (especially for Asian populations of LB-causing genospecies) which can be utilized in future lab-based transmission studies to determine how further variability can lead to adaptation or human pathogenicity in these bacteria.