Antimicrobials: Modes of action and mechanisms of resistance
Antimicrobials: Modes of action and mechanisms of resistance
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DOI：
10.1080/10915810305089
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发表时间：
2003-03-01
影响因子：
2.2
通讯作者：
White, DG
中科院分区：
文献类型：
--
作者：
McDermott, PF;Walker, RD;White, DG
经过60年抗生素的广泛使用，人类和动物来源的细菌性病原体对许多抗菌素的耐药性越来越强。抗菌素耐药性通过有限的机制发展：(a)细菌细胞壁/膜的渗透性改变，这限制了抗菌素进入靶点；(b)抗微生物药物从细胞中主动外排；(c)靶位点突变；(d)抗菌剂的酶修饰或降解；(e)获得替代药物抑制的代谢途径。许多细菌抗菌素耐药性表型是由于获得外部基因而产生的，这些基因可能提供对一整类抗菌素的抗性。这些基因通常与称为质粒的大型可转移染色体外DNA元件相关，质粒上可能有其他可移动的DNA元件，如转座子和整合子。一系列不同的耐药基因可能积聚在一个单一的移动元件上，从而出现通过单一遗传事件获得多种抗生素耐药的情况。细菌种群在适应有毒环境方面的多样性，以及它们交换DNA的能力，表明抗生素耐药性是一种不可避免的生物现象，可能会继续成为一个慢性医学问题。成功管理现有的抗菌素并继续开发新的抗菌素，对于保护人类和动物健康免受细菌性病原体的侵害至关重要。
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.