Language

English

Publication Date

9-1-2024

Journal

Nature Microbiology

DOI

10.1038/s41564-024-01747-1

PMID

38965331

PMCID

PMC11585081

PubMedCentral® Posted Date

3-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Enterohemorrhagic Escherichia coli, Virulence, Type III Secretion Systems, Enterococcus faecalis, Adenine, Animals, Gene Expression Regulation, Bacterial, Escherichia coli Proteins, Mice, Escherichia coli Infections, Humans, Hemolysin Proteins, Host-Pathogen Interactions, Coculture Techniques, Enterocytes, Xanthine, Hypoxanthine, Virulence Factors, Gastrointestinal Microbiome

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.