Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide-resistant enterococci
Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide-resistant enterococci
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DOI：
10.1046/j.1365-2958.1996.00617.x
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发表时间：
1996-07-01
影响因子：
3.6
通讯作者：
Courvalin, P
中科院分区：
文献类型：
--
作者：
Arthur, M;Depardieu, F;Courvalin, P
来自屎肠球菌BM 4147的转座子Tn 1546介导对糖肽类抗生素万古霉素和替考拉宁的高水平耐药性。Tn 1546编码合成D-丙氨酰-D-乳酸（D-Ala-D-Lac）的脱氢酶（VanH）和连接酶（VanA）、水解D-Ala-D-Ala的D，D-二肽酶（VanX）和控制vanHAX操纵子转录的双组分调节系统（VanR-VanS）。测试携带vanRSHAX簇的各种拷贝数的粪肠球菌菌株以确定对糖肽的抗性水平、相应抗性基因的表达水平和不同细胞质肽聚糖前体的相对比例之间是否存在相关性。vanHAX操纵子的转录增加与D-Ala-D-Lac掺入肽聚糖前体的增加相关，从而损害D-Ala-D-Ala，并且与万古霉素抗性水平的逐渐增加相关。替考拉宁耐药需要更完全消除含D-Ala-D-Ala的前体。也由Tn 1546编码的VanY和VanZ蛋白不是vanHAX操纵子调节的效应物，但分别导致万古霉素和替考拉宁耐药性。在监管水平的差异占表型多样性获得性糖肽抗性的生产D-缺乏结束的前体。
Transposon Tn1546 from Enterococcus faecium BM4147 mediates high-level resistance to the glycopeptide antibiotics vancomycin and teicoplanin. Tn1546 encodes a dehydrogenase (VanH) and a ligase (VanA) that synthesize D-alanyl-D-lactate (D-Ala-D-Lac), a D,D-dipeptidase (VanX) that hydrolyses D-Ala-D-Ala and a two-component regulatory system (VanR-VanS) that controls transcription of the vanHAX operon. Strains of Enterococcus faecalis harbouring various copy numbers of the vanRSHAX cluster were tested to determine if there was a correlation between the levels of resistance to glycopeptides, the levels of expression of the corresponding resistance genes and the relative proportions of the different cytoplasmic peptidoglycan precursors. Increased transcription of the vanHAX operon was associated with increased incorporation of D-Ala-D-Lac into peptidoglycan precursors to the detriment of D-Ala-D-Ala, and with a gradual increase in the vancomycin-resistance levels. More complete elimination of D-Ala-D-Ala-containing precursors was required for teicoplanin resistance. The VanY and VanZ proteins also encoded by Tn 1546 were not effecters of the regulation of the vanHAX operon but contributed to vancomycin and teicoplanin resistance, respectively. Differences at the regulatory level accounted for phenotypic diversity in acquired glycopeptide resistance by production of D-lac-ending precursors.