Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50
Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50
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DOI：
10.1128/aac.44.9.2276-2285.2000
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发表时间：
2000-09-01
影响因子：
4.9
通讯作者：
Hiramatsu, K
中科院分区：
文献类型：
--
作者：
Cui, LZ;Murakami, H;Hiramatsu, K
金黄色葡萄球菌Mu50降低了对万古霉素的敏感性，细胞壁显著增厚，谷氨酰胺非酰胺化多肽比例增加。此外，Mu50还增强了参与细胞壁肽聚糖合成途径的谷氨酰胺合成酶和L谷氨酰胺D-果糖-6-磷酸转氨酶的活性。此外，在Mu50中观察到C-14标记的D-葡萄糖掺入细胞壁的水平显著增加。与金黄色Femc突变株S不同，Mu50中非酰胺化神经肽产量的增加并不是由于谷氨酰胺合成酶活性水平较低造成的，而是由于细胞对葡萄糖的生物利用增加来合成更多的肽聚糖而导致谷氨酰胺耗竭所致。在没有葡萄糖和谷氨酰胺的情况下，允许细胞合成细胞壁后，制备了具有不同细胞壁厚度和不同交联度的细胞，对这些细胞的敏感性测试表明，细胞壁厚度与万古霉素耐药程度密切相关。细胞壁对万古霉素分子的亲和力捕获和结合的万古霉素分子对肽聚糖外层的堵塞被认为是MU50对万古霉素耐药的机制，非酰胺化多肽比例的增加可能是导致MU50细胞与万古霉素结合的交联度降低和亲和力增加的原因之一。
Staphylococcus aureus Mu50, which has reduced susceptibility to vancomycin, has a remarkably thickened cell wall with an increased proportion of glutamine nonamidated muropeptides. In addition, Mu50 had enhanced glutamine synthetase and L-glutamine D-fructose-6-phosphate aminotransferase activities, which are involved in the cell-wall peptidoglycan synthesis pathway. Furthermore, significantly increased levels of incorporation of C-14-labeled D-glucose into the cell wall was observed in Mu50. Unlike a femC mutant S, aureus strain, increased levels of production of nonamidated muropeptides in Mu50 was not caused by lower levels of glutamine synthetase activity but was considered to be due to the glutamine depletion caused by increased glucose utilization by the cell to biosynthesize increased amounts of peptidoglycan. After the cells were allowed to synthesize cell wall in the absence or presence of glucose and glutamine, cells with different cell-wall thicknesses and with cell walls with different levels of cross-linking were prepared, and susceptibility testing of these cells demonstrated a strong correlation between the cell-wall thickness and the degree of vancomycin resistance. Affinity trapping of vancomycin molecules by the cell wall and clogging of the outer layers of peptidoglycan by bound vancomycin molecules were considered to be the mechanism of vancomycin resistance of Mu50, The reduced cross-linking and the increased affinity of binding to vancomycin of the Mu50 cell mall presumably caused by the increased proportion of nonamidated muropeptides may also contribute to the resistance to some extent.