Bacterial Mercury Resistance Reveals a Robust Species-Structured Human Antimicrobial Mobilome

Antimicrobial resistance (AMR) is increasingly recognized as an ecological and evolutionary phenomenon that extends beyond clinical environments. Despite the predominant focus on antibiotics, bacterial metal resistance genes are among the oldest and most widespread adaptive antimicrobial systems, yet their distribution within human-associated microbial communities remains poorly characterized. Here, we investigated the ecology of mercury (Hg) resistance in children from a birth cohort with relatively high Hg exposure. Fecal samples from 234 children aged 4-8 years were analyzed using culture-based screening, whole-genome sequencing, and comparative analyses of metal- and antibiotic-resistance determinants and associated mobile genetic elements (MGEs). Hg-resistance was detected in 79.7% of samples, with HgR Enterobacterales isolated from 57% of children. Hair mercury concentrations were not associated with carriage. Sequencing revealed a phylogenetically diverse collection dominated by Escherichia spp. (61%). Hg resistance was mediated by 79 mer operons primarily associated with Tn21, Tn1696, and Tn5053 families circulating on chromosomes and a highly diverse plasmidome. Both rare and globally distributed plasmids related to foodborne, animal, and clinical Enterobacterales were identified. Metal resistance determinants exhibited strong taxonomic structuring, with Escherichia enriched in iron-uptake systems and siderophores whereas non-Escherichia taxa carried multimetal resistance operons. These findings indicate that Hg-resistance is shaped by ecological interactions and MGEs, becoming partially decoupled from contemporary Hg-exposure and bacterial community composition. The human gut therefore serves as an important reservoir linking environmental metal resistance to the broader evolution of AMR and provides insight into the baseline resistome and plasmidome of human populations.