Mobile Resistance Genes in Archaea: Genomic Evidence and One Health Implications

Archaea and bacteria share a close phylogenetic relationship and are both ubiquitous environmental components that exchange functional genes. However, it remains unclear how this evolutionary proximity and gene flow influence the carriage of antimicrobial resistance (AMR) genes in archaea or their role in AMR development in co-localised bacterial pathogens. This study investigated the diversity and abundance of antimicrobial resistance genes (ARGs) in archaeal genomes to clarify their role in AMR transmission, particularly through horizontal gene transfer (HGT).

Archaeal genomes from the Genome Taxonomy Database (v2.4.1, release 220), including 10,740 metagenome-assembled (MAGs), 1,601 pure-culture (WGS) and 136 single-cell (SAG) genomes, were screened for ARGs using PanRes (v1.0.2). A total of 47 ARGs were identified in MAGs, 111 in WGS and one in SAG, predominantly distributed within Methanobacteria, Halobacteria, and Thermoproteia, and typically isolated from host-associated samples, high-salinity waters or hot springs. Of these, 34% (MAGs) and 76.9% (WGS/SAG) were biocide or metal ARGs. Using mobileOG-db, 13 mobile genetic elements (MGEs) were identified adjacent to 16 ARGs across the dataset, suggesting potential HGT, particularly in strains from environmental or host-associated samples. Ongoing work involves validating potential HGT between archaea and bacteria through comparative genomic analyses and integrating biosample metadata to trace transfer pathways and ecological distributions, clarifying archaeal contributions to AMR transmission across domains of life.

This study highlights archaea as an overlooked but potentially significant reservoir of mobile ARGs within the One Health continuum, offering new insights into AMR gene exchange and strategies to mitigate global AMR risks.