Salmonella enteritidis:: AmpC plasmid-mediated inducible β-lactamase (DHA-1) with an ampR gene from Morganella morganii
Salmonella enteritidis:: AmpC plasmid-mediated inducible β-lactamase (DHA-1) with an ampR gene from Morganella morganii
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DOI：
10.1128/aac.42.9.2352
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发表时间：
1998-09-01
影响因子：
4.9
通讯作者：
Philippon, A
中科院分区：
文献类型：
--
作者：
Barnaud, G;Arlet, G;Philippon, A
DHA-1是一种来自单一临床分离的肠炎沙门氏菌的质粒介导的头孢菌素酶，它对头孢氨苄和头孢他啶以及头孢霉素类抗生素(头孢西丁和莫沙拉坦)具有耐药性，这种耐药性可转移到大肠杆菌HB101中。扩散法观察到头孢西丁与氨曲南之间存在拮抗作用。用携带ampD基因的pNH5基因(其产物降低ampC的表达水平)转化接合菌株，头孢西丁的最低抑菌浓度下降了8倍。获得了一株具有拮抗作用的AmpC酶敏感性相同的克隆，即E.coliJM101(pSAL2-ind)，并测定了其核苷酸序列。它含有一个开放阅读框，与摩根摩根菌的ampC基因序列同源性为98.7%。DNA序列分析还发现了AmpC基因上游的一个基因，该基因的序列与摩根分枝杆菌的AmpR基因部分序列(435bp)有97%的同源性。该基因编码的蛋白质具有典型的LysR家族转录激活因子的氨基末端DNA结合域。此外，AmpC基因和AMPR基因之间的顺反子间隔区与摩根分枝杆菌DNA中相应区域的同源性为98%。酶诱导和凝胶迁移率改变实验表明AMPR具有功能。从肠炎沙门氏菌分离株的DNA Southern印迹中也检测到AMPG基因。这些发现表明，这种可诱导的质粒型AmpC酶，DHA-1，可能起源于摩根分枝杆菌。
DHA-1, a plasmid-mediated cephalosporinase from a single clinical Salmonella enteritidis isolate, conferred resistance to oxyimino-cephalosporins (cefotaxime and ceftazidime) and cephamycins (cefoxitin and moxalactam), and this resistance was transferable to Escherichia coli HB101. An antagonism was observed between cefoxitin and aztreonam by the diffusion method. Transformation of the transconjugant E. coli strain with plasmid pNH5 carrying the ampD gene (whose product decreases the level of expression of ampC) resulted in an eightfold decrease in the MIC of cefoxitin. A clone with the same AmpC susceptibility pattern with antagonism was obtained, clone E. coli JM101(pSAL2-ind), and its nucleotide sequence was determined. It contained an open reading frame with 98.7% DNA sequence identity with the ampC gene of Morganella morganii. DNA sequence analysis also identified a gene upstream of ampC whose sequence was 97% identical to the partial sequence of the ampR gene (435 bp) from M. morganii. The gene encoded a protein with an amino-terminal DNA-binding domain typical of transcriptional activators of the LysR family. Moreover, the intercistronic region between the ampC and ampR genes was 98% identical to the corresponding region from M. morganii DNA. AmpR was shown to be functional by enzyme induction and a gel mobility-shift assay. An ampG gene was also detected in a Southern blot of DNA from the S. enteritidis isolate. These findings suggest that this inducible plasmid-mediated AmpC type beta-lactamase, DHA-1, probably originated from M. morganii.