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[革兰氏阴性菌的β-内酰胺酶:永不停歇的发条装置!]

[Beta-lactamases of Gram negative bacteria: never-ending clockwork!].

作者信息

Philippon A, Arlet G

机构信息

Service de bactériologie, CHU Cochin, AP-HP, Paris.

出版信息

Ann Biol Clin (Paris). 2006 Jan-Feb;64(1):37-51.

Abstract

The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.

摘要

随着各种质粒编码的、或编码新型β-内酰胺酶的基因盒或整合子的发现,对包括第三代头孢菌素(3GC)和碳青霉烯类在内的广谱且高度稳定的β-内酰胺类药物的获得性耐药性不断增加并广泛传播,这始终是主要的耐药机制。为了解释对3GC的耐药性,随着TEM和SHV突变酶的不断出现,出现了几种类型的超广谱β-内酰胺酶(A类),即CTX-M型,至少有CTX-M-40,但也有其他非主要类型,如BES、GES、PLA、PER、VEB。包括3GC、头孢霉素和β-内酰胺酶抑制剂在内的更广泛耐药性与通常位于染色体上但可从肠杆菌属、弗氏柠檬酸杆菌、蜂房哈夫尼亚菌、摩根摩根菌、豚鼠气单胞菌转移的可转移头孢菌素酶(C类)的合成有关。此类基因编码以下类型:ACC-1、ACT-1、CFE-1、CMY组、DHA-1、FOX组、MIR-1、MOX-1。最后,对碳青霉烯类药物如亚胺培南的耐药性最初仅限于铜绿假单胞菌,然后扩展到鲍曼不动杆菌,最后扩展到肠杆菌,这与新型酶(B类、D类和A类)的产生有关,这些酶被命名为IMP、VIM、SME、GIM、OXA、KPC。沙门氏菌甚至来自动物源的沙门氏菌向越来越耐药的进化就是一个显著例子,对公共卫生构成巨大威胁。到目前为止,似乎有必要采用分子方法来鉴定此类酶的产生。最后,由于缺乏真正的新药,发现了一些β-内酰胺酶基因的前体,因此不仅在医学或兽医领域,而且在农业(包括例如水产养殖)中都必须严格控制β-内酰胺抗生素。

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