Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut.
Adaptation, Physiological
Animals
Clostridiales
Gastrointestinal Microbiome
/ physiology
Glycoproteins
Humans
Metabolic Networks and Pathways
/ genetics
Mice
Mice, Inbred C57BL
Mucins
/ metabolism
Mucus
/ metabolism
N-Acetylneuraminic Acid
/ analogs & derivatives
Neuraminidase
Oxo-Acid-Lyases
/ metabolism
Polysaccharides
/ metabolism
Recombinant Proteins
Ruminococcus
/ enzymology
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
20
04
2019
accepted:
12
09
2019
pubmed:
23
10
2019
medline:
1
7
2020
entrez:
23
10
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31636419
doi: 10.1038/s41564-019-0590-7
pii: 10.1038/s41564-019-0590-7
pmc: PMC6881182
mid: EMS84365
doi:
Substances chimiques
Glycoproteins
0
Mucins
0
Polysaccharides
0
Recombinant Proteins
0
2,7-anhydro-N-acetylneuraminic acid
95574-95-1
trans-sialidase
EC 3.2.1.-
Neuraminidase
EC 3.2.1.18
Oxo-Acid-Lyases
EC 4.1.3.-
N-acetylneuraminate lyase
EC 4.1.3.3
N-Acetylneuraminic Acid
GZP2782OP0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2393-2404Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P008895/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/00044452
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10353
Pays : United Kingdom
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