Laura DE NIES

A metagenomic perspective of antimicrobial resistance in a One Health context
The emergence and spread of antimicrobial resistance (AMR) is a global threat due to the inability to comprehensively treat bacterial infections. Resistant bacteria residing within human, animal and environmental reservoirs may spread from one to the other, at both local and global levels. Compounding this phenomenon, antimicrobial resistance genes (ARGs) can further disseminate within the microbial populations through horizontal gene transfer and can even spread from commensal species to pathogens. Therefore, AMR has the potential to rapidly become pandemic whereby it is no longer constrained by either geographical or human-animal borders. A One Health perspective characterizing the resistome in human, animal and environmental microbial reservoirs is therefore crucial to our understanding on the dissemination of AMR.
We performed high-resolution, quantitative metagenomic analyses on animal, environmental and human metagenomic datasets. Herein, we identified ARGs within and across biomes, and compared their identity and prevalence across the different microbial reservoirs. We found that human and animal microbial reservoirs carried the highest abundance of AMR, while environmental reservoirs encoded a greater diversity of unique ARGs. Additionally, resistance genes were contextualized to their localization on mobile genetic elements (MGEs) as well as their associated microbial taxa. Based on gene mobility, host pathogenicity and their association with human populations, we evaluated the risk factor of the individual ARGs. Consequently, we found that the majority of the ARGs were human-associated with a significant proportion encoded on MGEs. we identified MGE-encoded unique beta-lactam ARGs, that previously have not been reported in human metagenomes. Collectively, our findings reveal that a metagenomic perspective of AMR in a One Health context is crucial for identifying key reservoirs and potentially critical, yet novel human-associated ARGs.

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