Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), can persist in the host for decades without causing TB symptoms and can cause a latent infection, which is an intricate challenge of current TB control. The DosR regulon, which contains approximately 50 genes, is crucial in the non-replicating persistence of Mtb. tgs1 is one of the most powerfully induced genes in this regulon during Mtb non-replicating persistence. The gene encodes a triacyl glycerol synthase catalyzing synthesis of triacyl glycerol (TAG), which is proposed as an energy source during bacilli persistence. Here, western blotting showed that the Tgs1 protein was upregulated in clinical Mtb strains. To detect its physiological effects on mycobacterium, we constructed serial recombinant M. marinum including over-expressed Tgs1(Tgs1-H), reduced-expressed Tgs1(Tgs1-L), and wild type M. marinum strains as controls. Tgs1 over-expression did not influence M. marinum growth under aerobic shaking and in hypoxic cultures, while growth advantages were observed at an early stage under nutrient starvation. Transmission electron microscopy revealed more lipid droplets in Tgs1-H than the other two strains; the droplets filled the cytoplasm. Two-dimensional thin-layer chromatography revealed more phosphatidyl-myo-inositol mannosides in the Tgs1-H cell wall. To assess the virulence of recombinant M. marinum in the natural host, adult zebrafish were infected with Tgs1-H or wild type strains. Hypervirulence of Tgs1-H was characterized by markedly increased bacterial load and early death of adult zebrafish. Remarkably, zebrafish infected with Tgs1-H developed necrotizing granulomas much more rapidly and in higher amounts, which facilitated mycobacterial replication and dissemination among organs and eventual tissue destruction in zebrafish. RNA sequencing analysis showed Tgs1-H induced 13 genes differentially expressed under aerobiosis. Among them, PE_PGRS54 (MMAR_5307),one of the PE_PGRS family of antigens, was markedly up-regulated, while 110 coding genes were down-regulated in Tgs1-L.The 110 genes included 22 member genes of the DosR regulon. The collective results indicate an important role for the Tgs1 protein of M. marinumin progression of infection in the natural host. Tgs1 signaling may be involved in a previously unknown behavior of M. marinum under hypoxia/aerobiosis.

结核分枝杆菌（TB）的病原体结核分枝杆菌（Mtb）可以在宿主中持续数十年而不引起TB症状，并且可以引起潜伏感染，这是当前控制TB的复杂挑战。DosR regulon包含大约50个基因，对Mtb的非复制持久性至关重要。在Mtb非复制持续过程中，tgs1是该调节子中最有力的诱导基因之一。该基因编码催化三酰基甘油（TAG）合成的三酰基甘油合酶，这被认为是细菌持续过程中的一种能源。在这里，蛋白质印迹显示Tgs1蛋白在临床Mtb中被上调株。为了检测其对分枝杆菌的生理作用，我们构建了一系列重组海藻分支杆菌，包括过表达的Tgs1（Tgs1-H），低表达的Tgs1（Tgs1-L）和野生型海藻分支杆菌菌株作为对照。Tgs1的过表达不会影响有氧摇动和低氧培养中的海藻分枝杆菌的生长，而在营养不足的早期阶段则观察到了生长优势。透射电子显微镜显示，Tgs1-H中的脂滴多于其他两个菌株。液滴充满细胞质。二维薄层色谱显示Tgs1-H细胞壁中有更多的磷脂酰-肌醇-甘露糖苷。评估重组M. marinum的毒力在自然宿主中，成年斑马鱼感染了Tgs1-H或野生型菌株。Tgs1-H的高毒力特征在于成年斑马鱼的细菌负荷显着增加和早期死亡。值得注意的是，被Tgs1-H感染的斑马鱼发展更快，更高数量的坏死性肉芽肿，这促进了分枝杆菌在器官之间的复制和传播，并最终破坏了斑马鱼的组织。RNA测序分析显示，Tgs1-H诱导的13个基因在需氧状态下差异表达。其中，PE_PGRS54（MMAR_5307PE_PGRS抗原家族之一）被显着上调，而Tgs1-L中110个编码基因被下调.110个基因包括DosR regulon的22个成员基因。共同的结果表明，M。marinum的Tgs1蛋白在自然宿主感染过程中起着重要作用。Tgs1信号可能参与缺氧/好氧下海藻分枝杆菌的先前未知行为。