The function of heavy metals and antibiotics in the co-selection of plasmid-borne environmental resistance genes

Abstract

Heavy metal contamination contributes to the dissemination and persistence of antibiotic resistance genes (ARGs) in environmental reservoirs. The overlapping presence of antibiotics and metals, along with shared resistance mechanisms, suggests a co-evolution of resistance traits. While models of metal-antibiotic co-selection exist, the specific roles of individual metals, microbial taxa, genetic elements, and environmental contexts remain poorly quantified.

This study investigates co-selection by examining plasmid-borne resistance genes from metal-impacted sites at Lake Macquarie (NSW, Australia). A diverse set of plasmids conferring resistance to copper, zinc, cobalt, cadmium, and arsenic was recovered; two-thirds also carried ARGs, indicating co-resistance. However, many ARGs lacked detectable resistance phenotypes. A key exception was a novel polymyxin resistance gene, mcr-12.1, identified as the first of a new mcr lineage. The mcr-12.1 gene conferred resistance in Pigmentiphaga litoralis, Acinetobacter baumannii, Pseudomonas aeruginosa, and Pseudomonas protegens.

Incomplete plasmid sequences from metagenomic data revealed additional resistance gene homologues, though their functionality remains to be confirmed.

To simulate co-selection, the native sediment bacterial community was exposed to arsenite and spectinomycin. Arsenite exposure increased spectinomycin resistance, consistent with co-selection, though the underlying genetic mechanism remains unclear.

This work underscores the link between anthropogenic metal pollution and environmental ARGs with potential clinical relevance. It highlights the need for antimicrobial resistance management strategies rooted in a One Health framework.