EXPLORING CO-INFECTIONS IN THE GASTROINTESTINAL TRACT: DISSECTING THE INTERACTION BETWEEN FUSOBACTERIUM NUCLEATUM AND CLOSTRIDIODES DIFFICILE

Abstract Background Clostridioides difficile is a common healthcare associated pathogen in U.S. hospitals, incurring billions of dollars treatment costs each year. Microbiome analysis C. infected (CDI) patients have revealed alterations the gut microbiota. It has been speculated that select members this altered microbiota may influence pathogenesis. known to reside intestinal mucus layer, but at present interactions between and other mucus-associated bacteria are poorly defined. To address these gaps knowledge, we focused on an entirely human-centered approach, employing human-derived MUC2, fecal bioreactors patient samples. We hypothesized would promote colonization biofilm formation. Methods & Results create model human layer microbiota, developed bioreactor system with MUC2-coated coverslips. Bioreactors were inoculated healthy feces, treated clindamycin mimic CDI. was found colonize form biofilms coverslips 16S rRNA sequencing unique profile substantial co-colonization Fusobacterium. Consistent our data, publicly available datasets stool samples subset infection harbored high levels F. nucleatum OTUs. also isolated microbes from adult pediatric IBD who positive for identified co-localization strains. RNAseq data significant changes chemotaxis surface adhesion genes following exposure metabolites. co-aggregate nucleatum; effect inhibited by blocking Fusobacterial adhesin RadD flagella. Moreover, ΔradD mutant lost ability aggregate difficile. Conversely, removal flagella significantly reduced interaction WT Addition enhanced formation, increasing extracellular polysaccharide. Conclusions Collectively, demonstrate role such as facilitating pathogenic