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

Abstract

Antimicrobial resistance (AMR) is increasingly recognised 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 characterised. Here, we investigated the occurrence of mercury (Hg) resistance and characterised the diversity of opportunistic pathogen species carrying mer genes, as well as their genetic contexts, and associated metal and antibiotic resistance determinants in children from a birth cohort with relatively high Hg exposure. Fecal samples from 234 children aged 4-8 years were analysed using culture-based screening, whole-genome sequencing, and comparative genomic analyses of 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. Plasmids carrying mer operons were highly related to others previously reported in foodborne, animal, and clinical Enterobacterales. Metal resistance determinants exhibited strong taxonomic structuring, with Escherichia enriched in iron-uptake systems and siderophores whereas non-Escherichia taxa carried multiple metal 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.