grant

Commensal control of C. difficile virulence

Organization BRIGHAM AND WOMEN'S HOSPITALLocation BOSTON, UNITED STATESPosted 1 Feb 2021Deadline 31 Jan 2027
NIHUS FederalResearch GrantFY2025Amino AcidsAminoacetic AcidAntibiotic AgentsAntibiotic DrugsAntibioticsBile AcidsBiological MarkersBiomassBody TissuesButyratesC bifermentansC diffC difficileC. bifermentansC. diffC. difficileC. difficile colitisCarbohydratesCarbonCausalityChlolincocinChlorlincocinClindamycinClostridioides difficileClostridioides difficile colitisClostridiumClostridium bifermentansClostridium difficileClostridium difficile colitisCoACoenzyme AColonComplexDehydratasesDehydrogenasesDiseaseDisorderEnvironmentEtiologyFermentationFree AssociationGene DeletionGeneralized GrowthGenesGeneticGerm-FreeGerminationGlycineGrowthHealth Care CostsHealth CostsHumanHydrasesHydro-LyasesHydrolaseHydrolase Family GeneHydrolase GeneIn VitroIndividualInfectionInfection preventionIntermediary MetabolismIntervention StudiesKnowledgeL-ProlineLeucineMediatingMetabolicMetabolic PathwayMetabolic ProcessesMetabolismMiceMice MammalsMicrobeMiscellaneous AntibioticModern ManMorbidityMorbidity - disease rateMurineMusNutrientOralOutcomeOxidantsOxidizing AgentsOxidoreductaseOxidoreductase GenePathway interactionsPatientsPopulationPrevent infectionProductionProlinePseudomembranous ColitisReductasesReproduction sporesResearch ResourcesResourcesSourceSporesSystemTestingTissue GrowthTissuesToxic MegacolonToxinVirulenceVirulentWeight GainWeight Increaseaminoacidbile saltsbio-markersbiologic markerbiological adaptation to stressbiomarkerbody weight gainbody weight increasecausationcommensal communitycommensal microbiomecommensal speciesdisease causationelectron acceptorfecal microbial transplantationfecal microbiome transplantationfecal microbiota transplantfecal microbiota transplantationfecal transplantfecal transplantationgene deletion mutationhuman florahuman microbial communitieshuman microbiotahuman microflorahuman-associated microbial communitieshuman-associated microbiotain vivointervention researchinterventional researchinterventional studyinterventions researchmetabolism measurementmetabolomicsmetabonomicsmicrobial consortiamicrobial floramicrobiotamicrofloramortalitymultispecies consortiamutantontogenypathogenpathwaypreventpreventingprogramsreaction; crisisresident commensalsstress responsestress; reactiontranscriptomicswt gain
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Full Description

Abstract: Clostridioides difficile, the etiology of pseudomembranous colitis, causes substantive
morbidity, mortality and close to $5 billion/year in US healthcare costs. Commensals provide

primary protection against C. difficile infections though the underlying mechanisms of action

remain ill-defined. We have identified individual bacterial species that provide long-term survival

against virulent C. difficile strains, and other species that can make the infection worse. Our

proposed aims will define specific commensal activities and commensal genes mediating these

effects on the pathogen, and test their functions in vivo, in mice carrying mouse vs human complex

microbiota, for the purposes of developing defined bacteriotherapeutics and biomarkers to predict

successful therapy.

Grant Number: 5R01AI153605-05
NIH Institute/Center: NIH

Principal Investigator: LYNN BRY

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