Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex
Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex
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DOI：
10.1038/s41598-019-39654-9
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发表时间：
2019-02-27
影响因子：
4.6
通讯作者：
Tonjum, Tone
中科院分区：
文献类型：
--
作者：
Birhanu, Alemayehu Godana;Yimer, Solomon Abebe;Tonjum, Tone
包括翻译后修饰(PTM)在内的多种调控机制赋予了结核分枝杆菌(Mtb)更简单的基因组和蛋白质组复杂性。糖基化等PTM在结核分枝杆菌适应过程中发挥着重要作用。用质谱仪分析了结核分枝杆菌复合体临床分离株(MTBC)3、4、5和7号谱系的糖蛋白质组图谱。在第1325个蛋白质中总共发现了2944个糖基化事件。这个数据集代表了迄今为止在结核分枝杆菌中发现的糖基化蛋白的最高数量。O-糖基化占识别事件的83%，而17%的位点是N-糖基化的。这是关于结核分枝杆菌和革兰氏阳性菌中N-连接蛋白糖基化的首次报道。总体而言，Mtb糖蛋白主要参与细胞膜生物合成、脂肪酸和脂肪代谢、双组分系统以及病原体与宿主的相互作用，这些都是暴露在细胞壁或位于细胞壁中的。定量糖蛋白质组学分析表明，与结核分枝杆菌适合性和生存相关的67个蛋白上的101个位点在四个谱系之间存在差异糖基化，其中%为细胞膜蛋白和膜蛋白。不同的糖基化模式可能有助于结核分枝杆菌谱系的表型变异。这项研究确定了几种临床上重要的膜相关糖脂蛋白，它们与诊断以及药物和疫苗发现有关。
Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb). PTMs such as glycosylation play a significant role in Mtb adaptive processes. The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry. A total of 2944 glycosylation events were discovered in 1325 proteins. This data set represents the highest number of glycosylated proteins identified in Mtb to date. O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated. This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria. Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall. Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins. The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages. The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.