The soil resistome: The anthropogenic, the native, and the unknown

•Antibiotic resistance (AR) is a major health concern.•Anthropogenic activities such as manure amendment can enhance soil AR reservoirs.•Non-impacted soils contain highly diverse collections of AR genes.•Native soil AR genes appear to be the source of many AR genes in pathogens.

Antibiotic resistance is a global phenomenon with severe epidemiological ramifications. Although the spread of antibiotic resistance is generally associated with selection derived from clinical use of antibiotics, recent studies have indicated that global proliferation of antibiotic resistance is also affiliated with natural environmental reservoirs, which can potentially transfer antibiotic resistance genes to clinically relevant bacteria via drinking water and the food chain. Terrestrial antibiotic resistance reservoirs are traditionally linked to anthropogenic activities such as manure and biosolid application, wastewater irrigation and agricultural application of antibiotic compounds that transmit residual concentrations of antibiotic compounds (that exert selective pressure), antibiotic resistant bacteria and antibiotic resistance genes to the soil. Although some evidence correlates between anthropogenic factors and elevated levels of antibiotic resistance in soil, it is becoming increasingly clear that un-impacted and pristine soils contain highly diverse and abundant levels of antibiotic resistant bacteria, which harbor a wide array of clinically-associated and novel antibiotic resistance genes. This has led to the resistome hypothesis, which speculates that many pathogen-associated antibiotic resistance genes originated in antibiotic-producing soil bacteria and reached pathogens via horizontal gene transfer. This review provides a holistic overview of how external and intrinsic factors influence soil antibiotic resistance.