2020
Structure and bioactivity of colibactin
Wernke KM, Xue M, Tirla A, Kim CS, Crawford JM, Herzon SB. Structure and bioactivity of colibactin. Bioorganic & Medicinal Chemistry Letters 2020, 30: 127280. PMID: 32527463, PMCID: PMC7309967, DOI: 10.1016/j.bmcl.2020.127280.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaStrands of DNABiosynthetic pathwaySecondary metabolitesColibactinMolecular-level explanationHuman gutAdenine residuesCell contactElectrophilic CyclopropanesCertain strainsBacteriaGenotoxic effectsHeterodimersDNABacterial cultureResiduesPathwayCleavageCellsStrandsGut
2019
Structure elucidation of colibactin and its DNA cross-links
Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, Shine EE, Wang W, Herzon SB, Crawford JM. Structure elucidation of colibactin and its DNA cross-links. Science 2019, 365 PMID: 31395743, PMCID: PMC6820679, DOI: 10.1126/science.aax2685.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaCell biology dataColibactin gene clusterCombination of geneticsComplex secondary metabolitesGene clusterIsotope labelingSecondary metabolitesBiology dataColibactinHuman gutTandem mass spectrometryBacteriaPhysiological effectsMass spectrometryStructure elucidationGutGeneticsDNAEnzymeChemical synthesisEscherichiaElucidationMetabolitesLabelingA 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
2017
ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance
Tripathi P, Shine EE, Healy AR, Kim CS, Herzon SB, Bruner SD, Crawford JM. ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance. Journal Of The American Chemical Society 2017, 139: 17719-17722. PMID: 29112397, PMCID: PMC6202678, DOI: 10.1021/jacs.7b09971.Peer-Reviewed Original ResearchConceptsGene productsBiosynthetic gene clusterSpecific mechanistic roleMolecular functionsGene clusterResidue mutantsHost bacteriaCancer formationColorectal cancer formationEscherichia coliCommensal Escherichia coliColibactinMechanistic roleHydrolase activityPrecolibactinsX-ray structureMolecular-level viewShare similaritiesElectrophilic CyclopropanesBacterial viabilityBacteriaHydrolaseGenotoxic effectsMutantsBiosynthesis
2010
Siderophores from Neighboring Organisms Promote the Growth of Uncultured Bacteria
D'Onofrio A, Crawford JM, Stewart EJ, Witt K, Gavrish E, Epstein S, Clardy J, Lewis K. Siderophores from Neighboring Organisms Promote the Growth of Uncultured Bacteria. Cell Chemical Biology 2010, 17: 254-264. PMID: 20338517, PMCID: PMC2895992, DOI: 10.1016/j.chembiol.2010.02.010.Peer-Reviewed Original ResearchConceptsCulturing of organismsUncultured isolatesUncultured bacteriaGrowth factorGrowth promotionCultured microbesCommunity establishmentBacterial speciesSediment biofilmHelper strainSiderophoresCultured organismsOrganismsLack of growthBacteriaPetri dishesSynthetic mediumSame environmentHabitatsIsolatesMicrobesSpeciesGrowthStrainsPromiscuityRegulating Alternative Lifestyles in Entomopathogenic Bacteria
Crawford JM, Kontnik R, Clardy J. Regulating Alternative Lifestyles in Entomopathogenic Bacteria. Current Biology 2010, 20: 69-74. PMID: 20022247, PMCID: PMC2821981, DOI: 10.1016/j.cub.2009.10.059.Peer-Reviewed Original ResearchConceptsAntibiotic productionMetabolic shiftNematode digestive tractBacterial proton motive forceBacterial metabolic regulationProton motive forceGenus PhotorhabdusTransporter PutPEntomopathogenic bacteriaInsect larvaeSmall moleculesInsecticidal toxinsNematode hostsInsect hemolymphBacterial pathwaysXenorhabdus nematophilaFungal competitorsDigestive tractL-prolineMetabolic regulationMotive forceHost environmentPhotorhabdusTT01Bacteria