2019
A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology
Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM, Palm NW. A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell 2019, 177: 1217-1231.e18. PMID: 31006530, PMCID: PMC6536006, DOI: 10.1016/j.cell.2019.03.036.Peer-Reviewed Original ResearchConceptsHost physiologyBioactive microbial metabolitesHuman gut bacteriaHost sensingProlific producersG proteinsGut microbiota metabolitesBlood-brain barrierL-PheMicrobial metabolitesOrphan GPCRsGut bacteriaColonic motilityInhibitor administrationMicrobiota metabolitesIntestinal microbiotaSmall moleculesDietary histidineBacteriaPhysiologyMicrobiota metabolomeMetabolitesGPR97Orthogonal approachGPCRs
2015
The colibactin warhead crosslinks DNA
Vizcaino MI, Crawford JM. The colibactin warhead crosslinks DNA. Nature Chemistry 2015, 7: 411-417. PMID: 25901819, PMCID: PMC4499846, DOI: 10.1038/nchem.2221.Peer-Reviewed Original ResearchConceptsDNA-damaging activityHost-microbe interactionsUncharacterized familyColibactin biosynthesisSmall moleculesHybrid pathwayCancer formationMode of actionDuplex DNACrosslinks DNAMicrobial metabolitesUnexpected modelHuman microbiotaSelect strainsMetabolomic analysisDNAPathwayEscherichia coli presentHuman colonLabeling studiesDisease statesDirect experimental evidenceHuman healthBiosynthesisColibactin