Antimicrobials: modes of action and mechanisms of resistance.
After six decades of widespread antibiotic use, bacterial pathogens of human and animal origin are becoming increasingly resistant to many antimicrobial agents. Antimicrobial resistance develops through a limited number of mechanisms: (a). permeability changes in the bacterial cell wall/membrane, which restrict antimicrobial access to target sites; (b). active efflux of the antimicrobial from the cell; (c). mutation in the target site; (d). enzymatic modification or degradation of the antimicrobial; and (e). acquisition of alternative metabolic pathways to those inhibited by the drug. Numerous bacterial antimicrobial resistance phenotypes result from the acquisition of external genes that may provide resistance to an entire class of antimicrobials. These genes are frequently associated with large transferable extrachromosomal DNA elements called plasmids, on which may be other mobile DNA elements such as transposons and integrons. An array of different resistance genes may accumulate on a single mobile element, presenting a situation in which multiple antibiotic resistance can be acquired via a single genetic event. The versatility of bacterial populations in adapting to toxic environments, along with their facility in exchanging DNA, signifies that antibiotic resistance is an inevitable biological phenomenon that will likely continue to be a chronic medical problem. Successful management of current antimicrobials, and the continued development of new ones, is vital to protecting human and animal health against bacterial pathogens.
Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, Maryland 20708, USA. pmcdermo@cvm.fda.gov
Patrick F
PF
McDermott
Robert D
RD
Walker
David G
DG
White
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001419:Bacteria / Q000235:genetics; D004251:DNA Transposable Elements / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000502:physiology*; D006801:Humans
D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D004269:DNA, Bacterial