Antimicrobial Resistance

Abstract

The discovery and development of antibiotics radically changed the treatment of bacterial infections and saved millions of lives. However, the evolution of antibiotic resistance has rendered many antibiotics ineffective. Antimicrobial resistance has also evolved to drugs aimed at inhibiting viruses, fungi, protozoa, and helminths. Antimicrobial resistance is conferred by several mechanisms: inactivation or degradation of drugs; target-site modification to reduce binding; reduced uptake into microbial cells; and increased efflux of drugs out of cells. Most antibiotic resistance genes in bacteria are in mobile genetic elements and acquired by horizontal gene transfer (HGT). Antibiotic resistance genes are found abundantly in bacterial populations (the resistome), particularly in soil, including in pristine soils and in 30,000-year-old permafrost. They likely evolved in bacteria to protect themselves from the toxic effects of the antibiotics they produced. The widespread use of antibiotics selects for high frequencies of antibiotic resistance. Antibiotics used clinically or in livestock production end up in the environment, selecting for antibiotic-resistant bacteria and HGT of resistance genes among many species. Exposure to antibiotics also selects for resistance in commensal bacteria, which can transfer resistance genes to clinical pathogens. Some commentators predict we are entering the post-antibiotic era because resistance is making antibiotics ineffective.