INDUCIBLE CEPHALOSPORINASE PRODUCTION IN CLINICAL ISOLATES OF ENTEROBACTER-CLOACAE IS CONTROLLED BY A REGULATORY GENE THAT HAS BEEN DELETED FROM ESCHERICHIA-COLI

INDUCIBLE CEPHALOSPORINASE PRODUCTION IN CLINICAL ISOLATES OF ENTEROBACTER-CLOACAE IS CONTROLLED BY A REGULATORY GENE THAT HAS BEEN DELETED FROM ESCHERICHIA-COLI
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DOI:
10.1002/j.1460-2075.1986.tb04704.x
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发表时间:
1986-12-01
期刊:
影响因子:
11.4
通讯作者:
COLE, ST
COLE, ST
中科院分区:
生物学1区
文献类型:
--
作者:
HONORE, N;NICOLAS, MH;COLE, ST

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头孢菌素超耐药阴沟肠杆菌菌株越来越多地从医院感染中分离出来。耐药性主要是由于编码头孢菌素酶的染色体ampC基因。与大肠杆菌相比,大肠杆菌是从位于frdD基因上游的启动子组成型表达ampC的。cloxacin显示可诱导的ampC表达。通过克隆ampC基因,表明连锁的遗传基因座ampR介导β-内酰胺。在不存在抗生素的情况下,30 500道尔顿的AmpR蛋白抑制ampC表达。ampR基因显示出高度紧凑的排列,位于差异表达的ampC基因和frd操纵子之间,并通过双功能转录终止子将其分离。ampR和ampC的启动子基本上重叠,mRNA分析表明,在诱导转录从ampC启动子大大增加,而从ampR没有。ampR基因两侧有两个序列同源区域,有人提出,祖先肠道细菌中这些区域之间的同源重组事件可能导致了ampR从大肠杆菌中缺失。coli基因组。
Cephalosporin hyper-resistant Enterobacter cloacae strains are isolated with increasing frequency from hospital infections. Resistance is principally due to the chromosomal ampC gene encoding a cephalosporinase. In contrast to Escherichia coli which expresses ampC constitutively from a promoter located in the upstream frdD gene, E. cloacae displays inducible ampC expression. By cloning the ampC gene it was shown that a linked genetic locus, ampR, mediated the induction by .beta.-lactams. In the absence of the antibiotic the 30 500 dalton AmpR protein represses ampC expression. The ampR gene shows a highly compact arrangement and is situated between the divergently expressed ampC gene and the frd operon from which it is separated by a bifunctional transcription terminator. The promoters for ampR and ampC substantially overlap and mRNA analyses showed that on induction transcription from the ampC promoter increased greatly whereas that from ampR did not. Two regions of sequence homology flank the ampR gene and it is proposed that a homologous recombination event between these in an ancestral enteric bacterium may have led to the deletion of ampR from the E. coli genome.