The study investigates the exchange of antibiotic resistance genes between soil bacteria and human pathogens using a high-throughput functional metagenomic approach. The researchers developed a method called PARFuMS to identify and characterize resistance genes from soil bacteria that can confer resistance to clinical pathogens. They found that multidrug-resistant soil bacteria contain resistance cassettes against five classes of antibiotics (β-lactams, aminoglycosides, amphenicols, sulfonamides, and tetracyclines) with perfect nucleotide identity to genes from diverse human pathogens. This identity includes non-coding regions and mobilization sequences, indicating both lateral gene transfer and a mechanism for the dissemination of antibiotic resistance. The study highlights the clinical importance of the soil resistome and suggests that soil can be a direct source of pathogenic resistance genes, emphasizing the need to understand the role of environmental reservoirs in the global spread of antibiotic resistance.The study investigates the exchange of antibiotic resistance genes between soil bacteria and human pathogens using a high-throughput functional metagenomic approach. The researchers developed a method called PARFuMS to identify and characterize resistance genes from soil bacteria that can confer resistance to clinical pathogens. They found that multidrug-resistant soil bacteria contain resistance cassettes against five classes of antibiotics (β-lactams, aminoglycosides, amphenicols, sulfonamides, and tetracyclines) with perfect nucleotide identity to genes from diverse human pathogens. This identity includes non-coding regions and mobilization sequences, indicating both lateral gene transfer and a mechanism for the dissemination of antibiotic resistance. The study highlights the clinical importance of the soil resistome and suggests that soil can be a direct source of pathogenic resistance genes, emphasizing the need to understand the role of environmental reservoirs in the global spread of antibiotic resistance.