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Publication
Antimicrobial resistance phylodynamics and source attribution under a One Health framework
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Authors
Abstract(s)
Antimicrobial resistance (AMR) is a significant public health threat and has recently been recognized as a One Health issue, reflecting the interconnected nature of human, animal, and environmental health. This thesis aimed to increase knowledge on the burden, drivers and transmission dynamics of AMR at the human-animal-environment interfaces, for which Staphylococcus aureus, wild ungulates and genomics were central.
Wastewater-based surveillance (WBS) of urban and hospital sewersheds by shotgun metagenomics depicted microbiota signatures of public health importance, while showing that the urban resistome is not restricted to clinically relevant pathogens, being strongly related with the most consumed antimicrobials in Europe.
Through molecular, phenotypic and ecological modelling analyses, we show that AMR in commensal Staphylococcus aureus strains from wild ungulates in Portugal is driven by agricultural land cover and livestock farming. We then generate and explore a large dataset of S. aureus draft genomes from wild ungulates to address with high resolution the hypotheses that wildlife colonization and AMR occurrence are related with human activities and that host adaptation is accompanied by genome diversification with phenotypic impacts. For source attribution purposes, we dissect host-informative mobile genetic elements (MGE) and, in parallel, perform ancestral host state reconstruction via phylodynamics. Based on cgMLST, we demonstrate high genomic similarity of S. aureus at the animal-human interface, with MGE biomarkers for host adaptation further supporting epidemiological connections. Phylodynamic inferences on relevant molecular types across Iberia indicate that several clonal lineages were widespread among humans before jumping to new hosts, highlighting recent spillover events from livestock to wildlife. Pangenome analyses retrieved S. aureus antimicrobial and heavy metals resistance determinants in the accessory genome.
This thesis provides new insights on AMR transmission across interfaces, encouraging environmental and animal surveillance to help curb AMR, and confirms that genomic data-driven approaches are powerful to track AMR trends and drivers.
Description
Keywords
Antimicrobial Resistance Transmission One Health Genomic Surveillance Staphylococcus aureus Wild Ungulates Transmissão da Resistência a Antimicrobianos Uma Só Saúde Vigilância Genómica Ungulados Selvagens