微生物群和肠道病原体之间的相互作用可以促进定植抵抗或增强发病机制。致病菌粪肠球菌通过上调 3 型分泌系统 (T3SS) 表达、效应器易位以及肠细胞上的附着和消除 (AE) 病变形成来增加肠出血性大肠杆菌 (EHEC) 毒力，但其背后的机制仍不清楚。通过类器官的共感染、代谢组学、补充实验和细菌遗传学，我们证明肠出血性大肠杆菌与粪肠球菌的共培养可增加黄嘌呤-次黄嘌呤途径的活性和腺嘌呤的生物合成。腺嘌呤或粪肠球菌促进 T3SS 基因表达，而转录组学显示 adeP 表达上调，adeP 编码腺嘌呤输入蛋白。从机制上讲，腺嘌呤缓解了 EHEC 中 T3SS 基因表达的高溶血素活性 (Hha) 依赖性抑制，并以 AdeP 依赖性方式促进 AE 病变形成。微生物群衍生的嘌呤，例如腺嘌呤，支持多种有益的宿主反应；然而，我们的数据显示，这种代谢物也会增加肠出血性大肠杆菌的毒力，凸显肠道中病原体-微生物-宿主相互作用的复杂性。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Interactions between microbiota and enteric pathogens can promote colonization resistance or enhance pathogenesis. The pathobiont Enterococcus faecalis increases enterohaemorrhagic E. coli (EHEC) virulence by upregulating Type 3 Secretion System (T3SS) expression, effector translocation, and attaching and effacing (AE) lesion formation on enterocytes, but the mechanisms underlying this remain unknown. Using co-infection of organoids, metabolomics, supplementation experiments and bacterial genetics, here we show that co-culture of EHEC with E. faecalis increases the xanthine-hypoxanthine pathway activity and adenine biosynthesis. Adenine or E. faecalis promoted T3SS gene expression, while transcriptomics showed upregulation of adeP expression, which encodes an adenine importer. Mechanistically, adenine relieved High hemolysin activity (Hha)-dependent repression of T3SS gene expression in EHEC and promoted AE lesion formation in an AdeP-dependent manner. Microbiota-derived purines, such as adenine, support multiple beneficial host responses; however, our data show that this metabolite also increases EHEC virulence, highlighting the complexity of pathogen-microbiota-host interactions in the gut.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.