葡萄糖胺-酸盐的多通道LC-MS/MS染色体的解卷:证据表明Staphylococcus aureus和Enterococcus faecium之间存在GlmS调控差异
Nitish R Mishra1, Amar Deep Sharma1, Shivani Gargvanshi1
1Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
Talanta open
|January 8, 2024
概括
使用MS/MS数据和非阴性解卷实现了像葡萄糖胺-6酸盐 (GlcN-6P) 和葡萄糖胺-1-酸盐 (GlcN-1P) 这样的类似分子的分解. 这种方法揭示了康治疗MRSA的GlcN-6P增加,表明GlmS调节.
科学领域:
- 分析化学 分析化学
- 生物化学 生物化学
- 微生物学 微生物学
背景情况:
- 同位体分析剂由于其相似的物理和化学性质,对染色学和质谱学分辨率构成重大挑战.
- 胺酸盐,如葡萄糖胺-6酸盐 (GlcN-6P) 和葡萄糖胺-1-酸盐 (GlcN-1P),是细菌细胞壁生物合成的关键中间体,但很难分离.
- 现有的分析方法很难分辨出这些极性和不保留的化合物.
研究的目的:
- 开发和验证一种新型的分析方法,用于分解异构性胺酸盐.
- 调查葡萄糖胺-6-酸盐 (GlcN-6P) 在抗甲素*黄金葡萄球菌* (MRSA) 对万科治疗的反应中的作用.
- 为了阐明MRSA中糖糖生物合成的调节,与菌素敏感性菌 (VSE) 和菌素耐药性菌 (VRE) 相比.
主要方法:
- 六胺酸盐 (GlcN-6P,GlcN-1P,GalN-1P) 的衍生与八酸无水化物.
- 确定C18列的染色学条件.
- 使用MS/MS碎片化模式和非负线性回归来解卷染色学上重叠的分析物.
- 开发的方法应用于MRSA,VSE和VRE的细菌提取物.
主要成果:
- 获得了衍生型GlcN-6P,GlcN-1P和GalN-1P的完整色谱分辨率.
- 非阴性解卷成功地解决了基于不同的MS/MS强度概况的共同排泄GlcN-1P和GalN-1P.
- 观察到GlcN-6P的显著增加3倍,在Vancomycin治疗的MRSA中,但在VSE或VRE中没有.
- 这表明GlcN-6P的合成酶GlmS的差异调节,作为对万科米辛的反应.
结论:
- 开发的MS/MS解卷法为解决复杂生物矩阵中的异构六胺-酸盐提供了强大的工具.
- 这些发现突出了一个特定的监管机制,涉及到GlmS在MRSA中对菌素的耐药性.
- 这项研究提供了对MRSA和VSE/VRE.之间独特的糖生物合成途径的见解.
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