Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme with transamidating activity. We report here that both expression and activity of TG2 are enhanced in mammalian epithelial cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 impairs bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e., hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis and protein O-GlcNAcylation. The correlation between TG2 transamidating activity and O-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain their own metabolic needs.

中文翻译：

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感染驱动的转谷氨酰胺酶 2 激活可促进上皮细胞中的葡萄糖摄取和己糖胺生物合成。

转谷氨酰胺酶 2 (TG2) 是一种普遍表达的酶，具有转酰胺酶活性。我们在此报告，在感染了专性细胞内细菌沙眼衣原体的哺乳动物上皮细胞中，TG2 的表达和活性均得到增强。TG2 的遗传或药理学抑制会损害细菌发育。我们表明 TG2 通过上调葡萄糖转运蛋白基因 GLUT-1 和 GLUT-3 的转录来增加葡萄糖输入。此外，TG2 激活驱动宿主中的一种特定的葡萄糖依赖性途径，即己糖胺生物合成。从机制上讲，我们在 TG2 的底物中鉴定了葡萄糖胺：6-磷酸果糖转氨酶 (GFPT)。TG2 对 GFPT 的修饰增加了其酶活性，导致更高水平的 UDP-N-乙酰氨基葡萄糖生物合成和蛋白质 O-GlcNAcylation。TG2 转酰胺活性与 O-GlcNAcylation 之间的相关性在受感染细胞中被破坏，因为细菌正在利用宿主己糖胺生物合成，特别是帮助它们分裂。总之，我们的工作将 TG2 确立为控制哺乳动物细胞中葡萄糖衍生代谢途径的关键参与者，这些细胞本身被沙眼衣原体劫持以维持其自身的代谢需求。