The antibiotic resistome: the nexus of chemical and genetic diversity

Key PointsThe antibiotic resistome is the collection of all the antibiotic resistance genes, including those usually associated with pathogenic bacteria isolated in the clinics, non-pathogenic antibiotic producing bacteria and all other resistance genes.Many bacterial genomes contain cryptic resistance genes that can confer resistance, but do not seem to have been selected in response to recent exposure to antibiotics. These represent a large reservoir of antibiotic resistance genes.The antibiotic resistance genes in environmental and other non-pathogenic bacteria share amino-acid sequence similarities and biochemical mechanisms with resistance elements in clinical isolates.Structural biology and protein biochemistry has revealed that antibiotic resistance has evolved from precursor proteins with other metabolic functions. The powerful selection pressure produced by the use of cytotoxic antimicrobial agents spurs the selection of resistance mechanisms from these precursors.Antibiotics are ancient, dating back hundreds of millions of years. Resistance is therefore equally ancient, and the number of genes in the resistome is a reflection of the continuous co-evolution of small molecules in natural environments and microbial genomes.