The Soil Nitrogen Resistome: A Systematic Review of the Impact of Nitrogen Fertilizers on the Proliferation of Antimicrobial Resistance Genes

Beyond the confines of clinical environments, the developing threat to public health due to antimicrobial resistance (AMR), is also being affected by the presence of antibiotic resistance genes (ARGs) in agricultural soils. These genes are carried by bacteria found in the soil which receive a nutrient boost from large amounts of nitrogen fertilizer used in global agricultural production. However, there is still considerable uncertainty about the role of nitrogen fertilizer in altering the soil's genetic makeup and its ability to support resistant bacterial populations. Therefore, this systematic review examined the relationships between nitrogen (N) fertilization practices and the amount and type of antibiotic resistance genes present in agricultural soils using data from 47 relevant scientific publications that include field experiments, mechanistic studies, and metagenomics analysis. Using meta-analyses to compare the effects of various types of nitrogen fertilizers, differing application rates, and varying methods of fertilization on the characteristics of soil bacterial communities and their genetic resistance capacity, the results show that the use of either ammonium or nitrate forms of nitrogen affect the composition of the resistome in soil, promote the accumulation of multi-drug resistance genes, and increase the horizontal gene transfer capacity. Further, changes in the composition of soil microbial communities driven by nitrogen fertilizers provide an environment conducive to the accumulation and spread of resistance genes through mobile genetic elements. This review emphasizes that sustainable agricultural intensification will require an understanding of nitrogen's role as an environmental selective pressure that increases antibiotic resistance beyond clinical usage. The data provided here suggest that current fertilization practices are potentially generating an optimal environment for the proliferation of resistance genes with important implications for food security, environmental health, and human medicine.