Context matters - the complex interplay between resistome genotypes and resistance phenotypes

Application of metagenomic functional selections to study antibiotic resistance genes is revealing a highly diverse and complex network of genetic exchange between bacterial pathogens and environmental reservoirs, which likely contributes significantly to increasing resistance levels in pathogens. In some cases, clinically relevant resistance genes have been acquired from organisms where their native function is not antibiotic resistance, and which may not even confer a resistance phenotype in their native context. In this review, we attempt to distinguish the resistance phenotype from the resistome genotype, and we highlight examples of genes and their hosts where this distinction becomes important in order to understand the relevance of environmental niches that contribute most to clinical problems associated with antibiotic resistance.