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Enterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent
Fernando H Martins1,2, Thibaut Rosay3, Anubama Rajan4
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature Microbiology
|July 4, 2024
Summary
The gut bacterium Enterococcus faecalis boosts the virulence of pathogenic E. coli (EHEC) by increasing adenine production. This metabolite enhances EHEC
Area of Science:
- Microbiology
- Gastroenterology
- Pathogen-Host Interactions
Background:
- Microbiota and enteric pathogen interactions influence gut health, impacting colonization resistance and pathogenesis.
- The pathobiont Enterococcus faecalis is known to enhance enterohaemorrhagic E. coli (EHEC) virulence, but the underlying mechanisms are unclear.
Purpose of the Study:
- To elucidate the mechanisms by which Enterococcus faecalis enhances EHEC virulence.
- To investigate the role of specific metabolites in mediating pathogen-microbiota-host interactions.
Main Methods:
- Co-infection models using organoids.
- Metabolomic analysis to identify key metabolic changes.
- Supplementation experiments and bacterial genetics to validate findings.
Main Results:
- Co-culture of EHEC with E. faecalis significantly increased xanthine-hypoxanthine pathway activity and adenine biosynthesis.
- Adenine, either supplemented or produced by E. faecalis, promoted Type 3 Secretion System (T3SS) gene expression and attaching and effacing (AE) lesion formation in EHEC.
- Adenine relieved High hemolysin activity (Hha)-dependent repression of T3SS gene expression and acted in an AdeP-dependent manner for AE lesion formation.
Conclusions:
- Microbiota-derived adenine enhances EHEC virulence by upregulating T3SS expression and promoting AE lesion formation.
- This study highlights the complex role of metabolites like adenine in modulating pathogen virulence within the gut environment.
- Understanding these interactions is crucial for deciphering pathogen-microbiota-host dynamics in the gut.
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