Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut

DOI: 10.1038/s41564-019-0590-7

Authors: Andrew Bell (Quadram Institute Bioscience) , Jason Brunt (Quadram Institute Bioscience; University of Cambridge) , Emmanuelle Crost (Quadram Institute Bioscience) , Laura Vaux (Quadram Institute Bioscience) , Ridvan Nepravishta (University of East Anglia) , C. David Owen (Diamond Light Source) , Dimitrios Latousakis (Quadram Institute Bioscience) , An Xiao (University of California) , Wanqing Li (University of California) , Xi Chen (University of California) , Martin A. Walsh (Diamond Light Source) , Jan Claesen (Lerner Research Institute) , Jesus Angulo (University of East Anglia) , Gavin H. Thomas (University of York) , Nathalie Juge (Quadram Institute Bioscience)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 14

State: Published (Approved)
Published: October 2019

Abstract: Sialic acid (N-acetylneuraminic acid (Neu5Ac)) is commonly found in the terminal location of colonic mucin glycans where it is a much-coveted nutrient for gut bacteria, including Ruminococcus gnavus. R. gnavus is part of the healthy gut microbiota in humans, but it is disproportionately represented in diseases. There is therefore a need to understand the molecular mechanisms that underpin the adaptation of R. gnavus to the gut. Previous in vitro research has demonstrated that the mucin-glycan-foraging strategy of R. gnavus is strain dependent and is associated with the expression of an intramolecular trans-sialidase, which releases 2,7-anhydro-Neu5Ac, rather than Neu5Ac, from mucins. Here, we unravelled the metabolism pathway of 2,7-anhydro-Neu5Ac in R. gnavus that is underpinned by the exquisite specificity of the sialic transporter for 2,7-anhydro-Neu5Ac and by the action of an oxidoreductase that converts 2,7-anhydro-Neu5Ac into Neu5Ac, which then becomes a substrate of a Neu5Ac-specific aldolase. Having generated an R. gnavus nan-cluster deletion mutant that lost the ability to grow on sialylated substrates, we showed that—in gnotobiotic mice colonized with R. gnavus wild-type (WT) and mutant strains—the fitness of the nan mutant was significantly impaired, with a reduced ability to colonize the mucus layer. Overall, we revealed a unique sialic acid pathway in bacteria that has important implications for the spatial adaptation of mucin-foraging gut symbionts in health and disease.

Journal Keywords: Enzymes; Glycobiology; Glycosides; Microbiome; Proteins

Diamond Keywords: Gut Microbiota; Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography , VMXi-Versatile Macromolecular Crystallography in situ

Added On: 24/10/2019 11:59

Discipline Tags:

Biochemistry Genetics Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)