The gate controlling cell wall synthesis in Staphylococcus aureus
The gate controlling cell wall synthesis in Staphylococcus aureus
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DOI：
10.1111/j.1365-2958.2004.04200.x
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发表时间：
2004-08-01
影响因子：
3.6
通讯作者：
Sugai, M
中科院分区：
文献类型：
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作者：
Komatsuzawa, H;Fujiwara, T;Sugai, M
葡萄糖胺-6-P在细胞壁合成和糖酵解之间占据中心位置。在导致肽聚糖前体形成的初始步骤中，葡糖胺-6-P被依次加工成UDP-N-乙酰葡糖胺，而为了进入糖酵解途径，葡糖胺-6-P被NagB异构化成果糖-6-P。尽管我们不能证明NagB活性，但nagB失活显著降低了生长。突变分析表明，那牙参与从N-乙酰葡糖胺-6-P形成葡糖胺-6-P，GlmS参与从果糖-6-P形成葡糖胺-6-P。glmS的失活阻止以葡萄糖作为唯一碳源的生长，其在与N-乙酰葡糖胺互补后恢复。在N-乙酰葡糖胺存在下，glmS的转录以及GlmS的量减少。这一点以及N-乙酰葡糖胺优先于葡萄糖掺入细胞壁材料表明，N-乙酰葡糖胺专门用于细胞壁合成，而葡萄糖同时用于细胞壁合成和糖酵解。这些观察进一步表明GlmS是金黄色葡萄球菌中导致葡萄糖到细胞壁合成的关键且唯一的酶，并且表明糖利用中存在严格的调节和等级。那牙、nagB或glmS的失活影响了S.金黄色葡萄球菌对细胞壁合成抑制剂的抗性，表明细胞壁前体形成的效率和抗性水平之间的相互依赖性。
Glucosamine-6-P occupies a central position between cell wall synthesis and glycolysis. In the initial steps leading to peptidoglycan precursor formation glucosamine-6-P is processed sequentially to UDP-N-acetylglucosamine, while to enter the glycolysis pathway, glucosamine-6-P is isomerized by NagB to fructose-6-P. Although we could not demonstrate NagB activity, nagB inactivation significantly reduced growth. Mutational analysis showed that NagA was involved in glucosamine-6-P formation from N-acetylglucosamine-6-P, and GlmS in that from fructose-6-P. Inactivation of glmS prevented growth on glucose as sole carbon source, which resumed after complementation with N-acetylglucosamine. Transcription of glmS as well as the amount of GlmS was reduced in the presence of N-acetylglucosamine. This and the preferential incorporation of N-acetylglucosamine over glucose into cell wall material showed that N-acetylglucosamine was used exclusively for cell wall synthesis, while glucose served both cell wall synthesis and glycolysis. These observations suggest furthermore GlmS to be the key and only enzyme leading from glucose to cell wall synthesis in Staphylococcus aureus, and show that there exists a tight regulation and hierarchy in sugar utilization. Inactivation of nagA, nagB or glmS affected the susceptibility of S. aureus to cell wall synthesis inhibitors, suggesting an interdependence between efficiency of cell wall precursor formation and resistance levels.