Bovine tuberculosis caused by Mycobacterium bovis remains a major cause of economic loss in cattle industries worldwide. However, the pathogenic mechanisms remain poorly understood. Post-translation modifications (PTM) such as phosphorylation play a crucial role in pathogenesis. While the change of transcriptome and proteome during the interaction between M. bovis and cattle were studied, there are no reports on the phosphoproteome change. We apply Tandem Mass Tag-based (TMT) quantitative proteomics coupled with immobilized metal-chelated affinity chromatography (IMAC) enrichment to obtain the quantified phosphorylation in vivo of M. bovis infected cattle lung tissue. The phosphorylated proteins are widespread in the nucleus, cytoplasm and plasma membrane. By using a change fold of 1.2, 165 phosphosites from 147 proteins were enriched, with 88 upregulated and 77 downregulated sites respectively. We further constructed the protein-protein interaction (PPI) networks of STAT3, SRRM2 and IRS-1 based on their number of differential phosphorylation sites and KEGG pathways. Similar patterns of gene expression dynamics of selected genes were observed in Mycobacterium tuberculosis infected human sample GEO dataset, implicating crucial roles of these genes in pathogenic Mycobacteria – host interaction. The first phosphorproteome reveals the relationship between bovine tuberculosis and glucose metabolism, and will help further refinement of target proteins for mechanistic study.

造成牛结核病牛分枝杆菌保持经济损失的全球牛产业的一大原因。但是，其致病机理仍知之甚少。翻译后修饰（PTM），例如磷酸化在发病机理中起关键作用。虽然研究了牛分枝杆菌和牛之间相互作用时转录组和蛋白质组的变化，但尚无关于磷酸化蛋白质组变化的报道。我们应用耦合与固定化金属亲和螯合层析法（IMAC）富集串联质谱基于标签（TMT）定量蛋白质组学，以获得量化的磷酸化在体内的牛分枝杆菌被感染的牛肺组织。磷酸化的蛋白质广泛分布于细胞核，细胞质和质膜中。通过使用1.2的变化倍数，来自147种蛋白质的165个磷酸位点被富集，分别具有88个上调的位点和77个下调的位点。基于它们的差异磷酸化位点的数量和KEGG途径，我们进一步构建了STAT3，SRRM2和IRS-1的蛋白质-蛋白质相互作用（PPI）网络。在结核分枝杆菌感染的人类样品GEO数据集中观察到选定基因的基因表达动态相似模式，这暗示了这些基因在致病性分枝杆菌中的关键作用–主机交互。第一个磷酸化蛋白质组揭示了牛结核与葡萄糖代谢之间的关系，并将有助于进一步精炼目标蛋白以进行机理研究。