Fusobacteriumnucleatum Adheres to Clostridioides difficile via the RadD Adhesin to Enhance Biofilm Formation in Intestinal Mucus.
Adhesins, Bacterial
/ genetics
Bacterial Adhesion
/ immunology
Biofilms
Bioreactors
/ microbiology
Clostridioides difficile
/ genetics
Clostridium Infections
/ immunology
Feces
/ microbiology
Flagella
/ genetics
Fusobacterium nucleatum
/ immunology
Gastrointestinal Microbiome
/ immunology
HT29 Cells
Humans
Intestinal Mucosa
/ immunology
Mucin-2
/ metabolism
Biofilm
Clostridioides difficile
MUC2
Mucus
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
05
10
2019
revised:
02
11
2020
accepted:
13
11
2020
pubmed:
24
11
2020
medline:
6
8
2021
entrez:
23
11
2020
Statut:
ppublish
Résumé
Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation. To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips. C difficile was found to colonize and form biofilms on MUC2-coated coverslips, and 16S rRNA sequencing showed a unique biofilm profile with substantial cocolonization with Fusobacterium species. Consistent with our bioreactor data, publicly available data sets and patient stool samples showed that a subset of patients with C difficile infection harbored high levels of Fusobacterium species. We observed colocalization of C difficile and F nucleatum in an aggregation assay using adult patients and stool of pediatric patients with inflammatory bowel disease and in tissue sections of patients with CDI. C difficile strains were found to coaggregate with F nucleatum subspecies in vitro; an effect that was inhibited by blocking or mutating the adhesin RadD on Fusobacterium and removal of flagella on C difficile. Aggregation was shown to be unique between F nucleatum and C difficile, because other gut commensals did not aggregate with C difficile. Addition of F nucleatum also enhanced C difficile biofilm formation and extracellular polysaccharide production. Collectively, these data show a unique interaction of between pathogenic C difficile and F nucleatum in the intestinal mucus layer.
Sections du résumé
BACKGROUND & AIMS
Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation.
METHODS
To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips.
RESULTS
C difficile was found to colonize and form biofilms on MUC2-coated coverslips, and 16S rRNA sequencing showed a unique biofilm profile with substantial cocolonization with Fusobacterium species. Consistent with our bioreactor data, publicly available data sets and patient stool samples showed that a subset of patients with C difficile infection harbored high levels of Fusobacterium species. We observed colocalization of C difficile and F nucleatum in an aggregation assay using adult patients and stool of pediatric patients with inflammatory bowel disease and in tissue sections of patients with CDI. C difficile strains were found to coaggregate with F nucleatum subspecies in vitro; an effect that was inhibited by blocking or mutating the adhesin RadD on Fusobacterium and removal of flagella on C difficile. Aggregation was shown to be unique between F nucleatum and C difficile, because other gut commensals did not aggregate with C difficile. Addition of F nucleatum also enhanced C difficile biofilm formation and extracellular polysaccharide production.
CONCLUSIONS
Collectively, these data show a unique interaction of between pathogenic C difficile and F nucleatum in the intestinal mucus layer.
Identifiants
pubmed: 33227279
pii: S0016-5085(20)35437-8
doi: 10.1053/j.gastro.2020.11.034
pmc: PMC7956072
mid: NIHMS1648624
pii:
doi:
Substances chimiques
Adhesins, Bacterial
0
MUC2 protein, human
0
Mucin-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1301-1314.e8Subventions
Organisme : NIAID NIH HHS
ID : U01 AI124290
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK123704
Pays : United States
Organisme : NIAID NIH HHS
ID : F32 AI136404
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK123195
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123278
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Informations de copyright
Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.
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