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Incorporating the genomic signature of environmental Mycobacterium bovis into transmission models of animal tuberculosis under a phylodynamics conceptual framework
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Animal tuberculosis (TB) remains an impacting animal and public health problem worldwide. This disease, affecting a wide range of mammal species, is primarily caused by Mycobacterium bovis. National authorities tackle animal TB mainly through culling programmes focused on cattle, overlooking transmission in wildlife and infection via the environment. This dissertation thus aimed at improving our understanding of the transmission processes of M. bovis/M. caprae at interfaces, via the development, application, and integration of novel tools to support data-driven intervention.
We developed eco-phylodynamic frameworks informed by pathogen whole genome sequencing (WGS) data, representing a multi-host transmission system in Portugal, at the livestock-wildlife interface. We found evidence for the co-circulation of M. bovis Eu1, Eu2, and Eu3 clonal complexes, enlightening Eu2 emergence and spread processes, showing most host transitions are intraspecific, while interspecific transmission between wildlife species, and between wild boar and cattle, are highly supported. We report the first phylodynamic analysis of Eu3 in Iberia and, via ecological modelling, we show most host transitions occurred toward higher temperature and precipitation and lower agriculture, road, and host density. Phylogeographic reconstruction evidenced frequent transmission between two ecological clusters, representing an ecological corridor of unrecognised importance.
Due to the historic inability to isolate environmental M. bovis, in this dissertation, an innovative single-cell workflow was developed, enabling quantification and sorting of viable and dormant M. bovis cells from natural substrates, showing widespread environmental contamination in animal aggregation spots. Whole genome enrichment and WGS enabled assessment, for the first time, of phylogenomic relatedness of environmental and animal M. bovis strains, showing these genomes are highly intertwined, with data supporting environmental contamination by shedding animals and pointing the environment as source of new infections.
This dissertation offers ground-breaking insights, with implications for animal TB policy formulation, advocating the inclusion of genomic and environmental surveillance in control programmes.
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Animal tuberculosis Mycobacterium bovis Multi-host system Environmental surveillance Genomic surveillance Tuberculose animal Mycobacterium bovis Sistema multi-hospedeiro Vigilância ambiental Vigilância genómica