Extrachromosomal resistance in Gram-negative organisms: The evolution of beta-lactamase
Extrachromosomal resistance in Gram-negative organisms: The evolution of beta-lactamase
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DOI：
10.1016/0966-842x(94)90611-4
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发表时间：
1994-01-01
影响因子：
15.9
通讯作者：
Jacoby, George A.
中科院分区：
文献类型：
--
作者：
Jacoby, George A.
细菌中的许多抗生素耐药性是由能够包装多个抗生素耐药性或毒力决定因素的质粒编码的，并可以促进它们在有机体之间的转移。质粒和B-内酰胺类细菌已经存在很长时间了。从前抗生素时代保存的细菌中回收了不含抗生素耐药决定因素的结合质粒，土壤中产生β-内酰胺酶的微生物一直是β-内酰胺酶细菌的主要防御手段，细菌克服青霉素、头孢菌素和相关的β-内酰胺类抗生素的影响。在抗生素时代，酶已经进化成更普遍，出现在新的宿主中，在更高的Icvcls中被表达，通过质粒获得，并改变催化性质，以增加对原本应该是非水解性底物的亲和力，或降低对β-内酰胺酶抑制剂的亲和力。从17世纪保存的植物标本中复苏2。这种酶当时的作用尚不清楚，但B-内酰胺酶现在是青霉素、头孢菌素和其他B-内酰胺类抗生素耐药的主要机制(参见第421页的抗生素词汇表)，这些药物的临床应用为这种酶的进化提供了强大的选择。
M uch of the antibiotic resistance in bacteria is encoded by plasmids that can package multiple antibiotic-resistance or virulence determinants and can facilitate their transfer between organisms. Plasmids and B-lactamascs have been around for a long time. Conjugative plasmids, free from antibioticresistance determinants, have been recovered from bacteria preserved from the pre-antibiotic era’, and soil organisms making P-lactamase have been b-Lactamascs are the major defense used by bacteria to overcome the effects of penicillins, cephalosporins and related b-lactam antibiotics. In the antibiotic era, the enzymes have evolved to become more prevalent, to appear in new hosts, to be exprcsscd at higher Icvcls, to be acquired by plasmids and to change catalytic properties to incrcasc affinity for what were meant to be nonhydrolysablc substrates or to reduce affinity for b-lactamase inhibitors. revived from plant specimens stored in the 17th century2. What the enzyme was doing then is not known, but B-lactamases are now the major mcchanism of resistance to penicillins, ccphalosporins and other B-lactam antibiotics (see p. 421 for a glossary of antibiotics), and the clinical use of these drugs has provided powerful selection for the evolution of this enzyme.