Molecular mechanisms of antibiotic resistance

• Published in: Nature reviews. Microbiology 2015-01, Vol.13 (1), p.42-51
• Main Authors: Blair, Jessica M. A., Webber, Mark A., Baylay, Alison J., Ogbolu, David O., Piddock, Laura J. V.
• Format: Article
• Language: English
• Subjects: 631/326/41/1969/2038; 631/553/338/22/1290; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacteria - drug effects; Bacteria - metabolism; Bacteria - pathogenicity; Cellular control mechanisms; Drug resistance in microorganisms; Drug Resistance, Bacterial; Genetic aspects; Genetic research; Global health; Inactivation; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiological research; Microbiology; Parasitology; review-article; Signal Transduction; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro3380

Key Points Antibiotic resistance is a global health emergency. Resistance mechanisms exist for all current antibiotics, and few new drugs are in development. Resistance can occur via a reduction in the intracellular concentration of drug, by target site alteration or protection and by the direct inactivation of antibiotics. The mobilization of resistance genes into pathogens is making the treatment of severe infections challenging owing to a lack of effective antibiotics. Our understanding of the molecular mechanisms of resistance has recently increased as a result of advances in systems biology, genomics and structural biology. New knowledge about antibiotic resistance should be used to inform the design of novel therapeutic agents that might not be subject to, or can circumvent, mechanisms of resistance. Antibiotic-resistant bacteria are causing a global health crisis. Here, the authors review recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics. This information should aid the discovery and development of new compounds that can circumvent or neutralize existing resistance mechanisms. Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.