Fusobacterium nucleatum Adheres to Clostridioides difficile via the RadD Adhesin to Enhance Biofilm Formation in Intestinal Mucus

核梭杆菌 微生物学 生物膜 梭杆菌 细菌粘附素 生物 粘液 粘蛋白 化学 艰难梭菌 细菌 毒力 分泌物 拟杆菌 牙龈卟啉单胞菌 基因 生物化学 遗传学 生态学
作者
Melinda A. Engevik,Heather A. Danhof,Jennifer M. Auchtung,Bradley T. Endres,Wenly Ruan,Eugénie Bassères,Amy C. Engevik,Qinglong Wu,Maribeth R Nicholson,Ruth Ann Luna,Kevin W. Garey,Sue E. Crawford,Mary K. Estes,Renate Lux,Mary Beth Yacyshyn,Bruce Yacyshyn,Tor Savidge,Robert A. Britton,James Versalovic
出处
期刊:Gastroenterology [Elsevier]
卷期号:160 (4): 1301-1314.e8 被引量:40
标识
DOI:10.1053/j.gastro.2020.11.034
摘要

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.
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