National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
Virulence. 2024 Dec;15(1):2435381. doi: 10.1080/21505594.2024.2435381. Epub 2024 Nov 27.
The intracellular pathogen can cause systemic diseases via its survival and replication in host macrophages. Xylose is the second most abundant sugar in nature and can use xylose as its sole carbon source for growth. However, whether xylose utilization contributes to the pathogenicity and intracellular growth of has not yet been determined. In this study, we observed that the xylose concentration in macrophages increased during infection. Moreover, there was an increase in expression of xylose catabolic genes ( and and the transcriptional regulatory gene of xylose metabolism () in macrophages, revealing the possibility of using host-accumulated xylose by for intracellular growth. Mutation of either or reduced replication in macrophages and attenuated the colonization of mouse systemic loci (e.g. the liver and spleen), indicating that xylose utilization promotes replication within macrophages and systemic infection in mice. Moreover, we found that xylose utilization by intracellular was activated by the cAMP-CRP complex upon detection of low glucose levels in the infected macrophages. Collectively, these findings reveal that although the available glucose decreases during infection, can use xylose, which accumulates in infected macrophages, as an alternative carbon source to promote intracellular replication and virulence.
胞内病原体可以在宿主巨噬细胞中生存和复制，从而引发全身性疾病。木糖是自然界中第二丰富的糖，能够将木糖作为其生长的唯一碳源加以利用。然而，木糖的利用是否有助于 的致病性和细胞内生长尚未确定。在本研究中，我们观察到在 感染期间巨噬细胞内的木糖浓度增加。此外，巨噬细胞中表达的 木糖分解代谢基因（ 和 以及木糖代谢的转录调控基因（）增加，表明 有可能利用宿主积累的木糖进行细胞内生长。 或 的突变减少了巨噬细胞中的 复制，并减弱了小鼠全身性定植部位（如肝脏和脾脏）的定植，表明木糖的利用促进了巨噬细胞内 和小鼠全身性感染的 复制。此外，我们发现，在感染的巨噬细胞中检测到低葡萄糖水平时，细胞内的木糖利用被 cAMP-CRP 复合物激活。总之，这些发现揭示了尽管在感染过程中可用的葡萄糖减少，但 可以利用感染巨噬细胞中积累的木糖作为替代碳源，促进细胞内复制和毒力。
