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TITLE:  Antimicrobials: modes of action and mechanisms of resistance
 
AUTHORS:  McDermott PF;Walker RD;White DG;
 
YEAR:  2003
 
JOURNAL ABBREV:  Int J Toxicol
 
MONTH:  Mar
 
TYPE:  JOUR
 
REFMAN INDEX:  235
 
JOURNAL FULL:  International journal of toxicology
 
VOLUME:  22
 
ISSUE:  2
 
START PAGE:  135
 
END PAGE:  143
 
KEYWORDS:  adverse effects;Animals;Anti-Bacterial Agents;Bacteria;Dna;DNA Transposable Elements;DNA,Bacterial;drug effects;Drug Resistance,Microbial;Environment;Food;genetics;Humans;Integrons;Maryland;Mutation;Phenotype;physiology;Plasmids;Research;veterinary;Veterinary Medicine;
 
ABSTRACT:  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
 
AFFILIATIONS:  Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, Maryland 20708, USA. pmcdermo@cvm.fda.gov
 
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