Bacterial phylogeny structures soil resistomes across habitats

Functional metagenomic selections for resistance to 18 antibiotics in 18 different soils reveal that bacterial community composition is the primary determinant of soil antibiotic resistance gene content. Antibiotic resistance genes readily move between unrelated bacteria in hospital settings, prompting speculation that the remarkable diversity of resistance genes in soil contributes to an increasing flow of antibiotic resistance from environmental to pathogenic organisms. This study refutes this notion. Kevin Forsberg et al. performed functional metagenomic selections for resistance to 18 antibiotics from a series of agricultural and grassland soils and find that soil bacteria rarely possess the sequence signatures of resistance gene exchange between species. It seems that particular organisms, rather than horizontally exchanged DNA elements, are the major disseminators of antibiotic resistance in the soil. Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil1,2,3, including genes identical to those in human pathogens4. Despite the apparent overlap between soil and clinical resistomes4,5,6, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown3. General metagenome functions often correlate with the underlying structure of bacterial communities7,8,9,10,11,12. However, ARGs are proposed to be highly mobile4,5,13, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions13,14. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2,895 ARGs we discovered were mostly new, and represent all major resistance mechanisms15. We demonstrate that distinct soil types harbour distinct resistomes, and that the addition of nitrogen fertilizer strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements (genes responsible for horizontal gene transfer between bacteria such as transposases and integrases) syntenic with ARGs were rare in soil by comparison with sequenced pathogens, suggesting that ARGs may not transfer between soil bacteria as readily as is observed between human pathogens. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny13,14.