Obligate intracellular bacteria such as Chlamydia trachomatis undergo a complex developmental cycle between infectious, non-replicative elementary-body and non-infectious, replicative reticulate-body forms. Elementary bodies transform to reticulate bodies shortly after entering a host cell, a crucial process in infection, initiating chlamydial replication. As Chlamydia fail to replicate outside the host cell, it is unknown how the replicative part of the developmental cycle is initiated. Here we show, using a cell-free approach in axenic media, that the uptake of glutamine by the bacteria is crucial for peptidoglycan synthesis, which has a role in Chlamydia replication. The increased requirement for glutamine in infected cells is satisfied by reprogramming the glutamine metabolism in a c-Myc-dependent manner. Glutamine is effectively taken up by the glutamine transporter SLC1A5 and metabolized via glutaminase. Interference with this metabolic reprogramming limits the growth of Chlamydia. Intriguingly, Chlamydia failed to produce progeny in SLC1A5-knockout organoids and mice. Thus, we report on the central role of glutamine for the development of an obligate intracellular pathogenic bacterium and the reprogramming of host glutamine metabolism, which may provide a basis for innovative anti-infection strategies.

专性细胞内细菌如沙眼衣原体在感染性、非复制性基本体和非感染性、复制性网状体形式之间经历复杂的发育循环。基本体在进入宿主细胞后不久转变为网状体，这是感染的关键过程，启动衣原体复制。由于衣原体无法在宿主细胞外复制，因此发育周期的复制部分是如何启动的尚不清楚。在这里，我们在无菌培养基中使用无细胞方法表明，细菌对谷氨酰胺的吸收对于肽聚糖合成至关重要，肽聚糖在衣原体中起作用复制。通过以依赖 c-Myc 的方式重新编程谷氨酰胺代谢，可以满足感染细胞对谷氨酰胺增加的需求。谷氨酰胺被谷氨酰胺转运蛋白 SLC1A5 有效吸收并通过谷氨酰胺酶代谢。干扰这种代谢重编程会限制衣原体的生长。有趣的是，衣原体未能在 SLC1A5 基因敲除类器官和小鼠中产生后代。因此，我们报告了谷氨酰胺在专性细胞内病原菌发育和宿主谷氨酰胺代谢重编程中的核心作用，这可能为创新的抗感染策略提供基础。