RadA, a MSCRAMM Adhesin of the Dominant Symbiote Ruminococcus gnavus E1, Binds Human Immunoglobulins and Intestinal
Marc Maresca1, Radia Alatou2, Ange Pujol1
1Aix Marseille University, CNRS, Centrale Marseille, ISM2, IM2B, 13007 Marseille, France.
Abstract:
Adhesion to the digestive mucosa is considered a key factor for bacterial persistence within the gut. In this study, we show that Ruminococcus gnavus E1 can express the radA gene, which encodes an adhesin of the MSCRAMMs family, only when it colonizes the gut. The RadA N-terminal region contains an all-β bacterial Ig-like domain known to interact with collagens. We observed that it preferentially binds human immunoglobulins (IgA and IgG) and intestinal mucins. Using deglycosylated substrates, we also showed that the RadA N-terminal region recognizes two different types of motifs, the protein backbone of human IgG and the glycan structure of mucins. Finally, competition assays with lectins and free monosaccharides identified Galactose and N-Acetyl-Galactosamine motifs as specific targets for the binding of RadA to mucins and the surface of human epithelial cells.
Insights
Ruminococcus gnavus E1 expresses RadA, a gut-colonizing adhesin, which binds human immunoglobulins and mucins. This adhesin targets specific galactose and N-acetyl-galactosamine motifs on host cells.
Area of Science:
- Microbiology
- Molecular Biology
- Gastroenterology
Background:
- Bacterial adhesion to the digestive mucosa is crucial for gut colonization.
- Ruminococcus gnavus is a gut bacterium whose adhesion mechanisms require further elucidation.
Purpose of the Study:
- To investigate the role of the RadA adhesin from Ruminococcus gnavus E1 in gut mucosal adhesion.
- To identify the specific molecular targets of the RadA adhesin.
Main Methods:
- Analysis of radA gene expression during gut colonization.
- Characterization of the RadA N-terminal region's binding properties using various substrates.
- Competition assays with lectins and monosaccharides to identify binding motifs.
Main Results:
- Ruminococcus gnavus E1 expresses the RadA adhesin specifically during gut colonization.
- The RadA N-terminal region binds human immunoglobulins (IgA, IgG) and intestinal mucins.
- RadA recognizes the protein backbone of IgG and glycan structures of mucins, specifically Galactose and N-Acetyl-Galactosamine motifs.
Conclusions:
- RadA is an MSCRAMM family adhesin critical for Ruminococcus gnavus E1 gut persistence.
- RadA mediates adhesion through interactions with host immunoglobulins and mucins via specific glycan recognition.
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