The article by Brodie F. Gillicatt and Nicholas V. Coleman explores the co-selection of antibiotic and heavy metal resistance in environmental bacteria. Heavy metals, such as cadmium, copper, and zinc, are significant contributors to the dissemination and persistence of antibiotic resistance genes in environmental reservoirs. The authors highlight the overlapping ranges of antibiotic and metal contamination and the similarities in their resistance mechanisms, suggesting an intertwined evolutionary history. Metal resistance genes are often genetically linked to antibiotic resistance genes, with plasmids, transposons, and integrons facilitating horizontal gene transfer (HGT) and the assembly of resistance elements. The review evaluates recent evidence from pure culture and metagenomic studies, focusing on the mechanisms of co-selection, including co-resistance, cross-resistance, and co-regulation. Co-resistance involves the simultaneous inheritance of resistance genes on the same mobile genetic element, while cross-resistance occurs when a single mechanism confers resistance to both a metal and an antibiotic. Co-regulation involves a unified transcriptional response to both agents. The authors discuss the challenges in defining and quantifying the molecular aspects of co-selection, particularly the importance of specific metals, environments, bacterial taxa, and other abiotic or biotic conditions. They emphasize the need for more in-depth characterizations using methodologies that confirm the functional expression of resistance genes and connect them to specific bacterial hosts. The review also examines the role of heavy metals in co-selection, noting that they have a broader sphere of influence than antibiotics due to their higher concentrations and persistence in the environment. Heavy metals are released from various anthropogenic sources, including industry, agriculture, and healthcare, and their presence often overlaps with antibiotic pollution. The toxic impacts of metals on microorganisms are influenced by factors such as concentration, ion valency, bioavailability, and environmental context. The authors provide a comprehensive overview of the resistome and mobilome, discussing the mechanisms of metal and antibiotic resistance, and the role of mobile genetic elements in the acquisition and transmission of resistance genes. They highlight the importance of high-throughput DNA sequencing and metagenomic data in advancing our understanding of co-selection. The review concludes with a discussion of the evidence for co-resistance and cross-resistance in various environmental contexts, including pristine, agricultural, and industrial environments. It emphasizes the need for further mechanistic investigations to confirm co-resistance and cross-resistance, particularly in the absence of apparent selection. The authors also discuss the potential implications of these findings for clinical interventions and site rehabilitation.The article by Brodie F. Gillicatt and Nicholas V. Coleman explores the co-selection of antibiotic and heavy metal resistance in environmental bacteria. Heavy metals, such as cadmium, copper, and zinc, are significant contributors to the dissemination and persistence of antibiotic resistance genes in environmental reservoirs. The authors highlight the overlapping ranges of antibiotic and metal contamination and the similarities in their resistance mechanisms, suggesting an intertwined evolutionary history. Metal resistance genes are often genetically linked to antibiotic resistance genes, with plasmids, transposons, and integrons facilitating horizontal gene transfer (HGT) and the assembly of resistance elements. The review evaluates recent evidence from pure culture and metagenomic studies, focusing on the mechanisms of co-selection, including co-resistance, cross-resistance, and co-regulation. Co-resistance involves the simultaneous inheritance of resistance genes on the same mobile genetic element, while cross-resistance occurs when a single mechanism confers resistance to both a metal and an antibiotic. Co-regulation involves a unified transcriptional response to both agents. The authors discuss the challenges in defining and quantifying the molecular aspects of co-selection, particularly the importance of specific metals, environments, bacterial taxa, and other abiotic or biotic conditions. They emphasize the need for more in-depth characterizations using methodologies that confirm the functional expression of resistance genes and connect them to specific bacterial hosts. The review also examines the role of heavy metals in co-selection, noting that they have a broader sphere of influence than antibiotics due to their higher concentrations and persistence in the environment. Heavy metals are released from various anthropogenic sources, including industry, agriculture, and healthcare, and their presence often overlaps with antibiotic pollution. The toxic impacts of metals on microorganisms are influenced by factors such as concentration, ion valency, bioavailability, and environmental context. The authors provide a comprehensive overview of the resistome and mobilome, discussing the mechanisms of metal and antibiotic resistance, and the role of mobile genetic elements in the acquisition and transmission of resistance genes. They highlight the importance of high-throughput DNA sequencing and metagenomic data in advancing our understanding of co-selection. The review concludes with a discussion of the evidence for co-resistance and cross-resistance in various environmental contexts, including pristine, agricultural, and industrial environments. It emphasizes the need for further mechanistic investigations to confirm co-resistance and cross-resistance, particularly in the absence of apparent selection. The authors also discuss the potential implications of these findings for clinical interventions and site rehabilitation.