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Characterization of a Four-Component Regulatory System Controlling Bacteriocin Production in Streptococcus
Alexis Proutière1,2,3, Laurence du Merle1,2, Bruno Périchon1,2
1Unité de Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur, Paris, France.
Mbio
|January 6, 2021
Summary
We identified a regulatory system controlling gallocin production in Streptococcus gallolyticus subsp. gallolyticus. This system involves a secreted peptide and two proteins that activate or repress bacteriocin gene transcription.
Area of Science:
- Microbiology
- Bacterial genetics
- Antimicrobial peptides
Background:
- *Streptococcus gallolyticus* subsp. *gallolyticus* is an opportunistic pathogen linked to colorectal cancer.
- This bacterium produces gallocin, a bacteriocin that aids colonization under tumoral conditions by outcompeting commensals.
- Understanding gallocin regulation is key to preventing pathogen colonization.
Purpose of the Study:
- Identify genes regulating gallocin production in *S. gallolyticus* subsp. *gallolyticus*.
- Characterize the roles of identified regulatory components (BlpH/BlpR, GSP, BlpS).
- Investigate gallocin functionality under simulated intestinal conditions.
Main Methods:
- Gene identification and characterization.
- Genome-wide transcriptome analysis (RNA-Seq).
- Electrophoretic mobility shift assays (EMSA) and footprinting assays.
- Competition experiments in gut microbiota medium.
Main Results:
- A four-component system (BlpH/BlpR, GSP, BlpS) regulates gallocin production.
- Gallocin-stimulating peptide (GSP) activates gallocin transcription via the BlpH/BlpR two-component system.
- BlpS represses gallocin transcription, likely by antagonizing BlpR.
- Both BlpR and BlpS bind to a conserved DNA operator sequence in promoter regions.
- Gallocin is functional under simulated *in vivo* intestinal conditions.
Conclusions:
- Gallocin expression is tightly controlled by quorum sensing and antagonistic LytTR proteins.
- The identified regulatory system (GSP-BlpH/BlpR-BlpS) is specific for bacteriocin production.
- Understanding this regulation is crucial for controlling *S. gallolyticus* subsp. *gallolyticus* colonization in tumoral environments.
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