2021
Escherichia coli small molecule metabolism at the host–microorganism interface
Gatsios A, Kim CS, Crawford JM. Escherichia coli small molecule metabolism at the host–microorganism interface. Nature Chemical Biology 2021, 17: 1016-1026. PMID: 34552219, PMCID: PMC8675634, DOI: 10.1038/s41589-021-00807-5.Peer-Reviewed Original ResearchConceptsSmall molecule metabolismE. coliHost-bacteria interfaceModel organismsHost-bacterial interactionsChemical arsenalMolecule metabolismEscherichia coliHuman microbiotaColiSmall molecule chemistryMetabolismCommon componentSignalingOrganismsBiologyDisease modulationCommensalEscherichiaHostPathogenic roleRoleMicrobiotaMembers
2020
Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli
Park HB, Wei Z, Oh J, Xu H, Kim CS, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford JM. Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli. Nature Microbiology 2020, 5: 1319-1329. PMID: 32719505, PMCID: PMC7581551, DOI: 10.1038/s41564-020-0763-4.Peer-Reviewed Original ResearchConceptsAnti-inflammatory interleukin-10Colitis mouse modelInflammatory bowel diseaseColitis symptomsBowel diseaseInterleukin-10Immunological markersPathogenic roleImmunomodulatory metabolitesImmunomodulatory phenotypeGastrointestinal tractMouse modelImmunological activityPrimary human tissuesDrug stressSubinhibitory levelsHuman tissuesEnvironmental isolatesCertain strainsMetabolic pathwaysMetabolitesPatientsEscherichia coliSymptomsIBDCellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli
Kim CS, Li JH, Barco B, Park HB, Gatsios A, Damania A, Wang R, Wyche TP, Piizzi G, Clay NK, Crawford JM. Cellular Stress Upregulates Indole Signaling Metabolites in Escherichia coli. Cell Chemical Biology 2020, 27: 698-707.e7. PMID: 32243812, PMCID: PMC7306003, DOI: 10.1016/j.chembiol.2020.03.003.Peer-Reviewed Original ResearchConceptsPlant-pathogen defense responsesPlant innate immune responsesPathogen defense responsesSmall molecule signalsEscherichia coliPersister cell formationStress-induced metabolitesPrimary human tissuesDefense responsesRedox stressorsInnate immune responseDistinct immunological responsesMolecule signalsMolecular studiesCell formationColiBacterial metabolitesDefensive responsesSmall moleculesPlantsHuman tissuesImmune responseImmunological responseInfection modelMetabolites
2018
Characterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening
Xue M, Shine E, Wang W, Crawford JM, Herzon SB. Characterization of Natural Colibactin–Nucleobase Adducts by Tandem Mass Spectrometry and Isotopic Labeling. Support for DNA Alkylation by Cyclopropane Ring Opening. Biochemistry 2018, 57: 6391-6394. PMID: 30365310, PMCID: PMC6997931, DOI: 10.1021/acs.biochem.8b01023.Peer-Reviewed Original ResearchConceptsGenotoxic secondary metabolitesMethionine auxotrophic strainsE. coliGut commensal Escherichia coliClb gene clusterColibactin biosynthesisElectrophilic CyclopropanesGene clusterDNA alkylationPrevious biosynthetic studiesSecondary metabolitesAuxotrophic strainsEscherichia coliCommensal Escherichia coliBiosynthetic studiesFirst identificationBiosynthesisColiColibactinPUC19 DNAIsotopic labelingNucleotidesDNATandem mass spectrometryCertain strains
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 effectsMutantsBiosynthesisDomain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis
Trautman EP, Healy AR, Shine EE, Herzon SB, Crawford JM. Domain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis. Journal Of The American Chemical Society 2017, 139: 4195-4201. PMID: 28240912, PMCID: PMC5831107, DOI: 10.1021/jacs.7b00659.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetasesPolyketide synthasesModular polyketide synthasesSite-directed mutagenesisCombination of genesCellular metabolic levelsColibactin biosynthesisMultidomain proteinsProtein domainsPeptide synthetasesCatalytic domainControl pathwaysProtein biochemicalPathway analysisCertain Escherichia coliComplete deletionHybrid pathwayEscherichia coliFunctional readoutBiosynthesisCatalytic mechanismCellular levelMetabolic levelPathwayGenes
2012
Small molecule perimeter defense in entomopathogenic bacteria
Crawford JM, Portmann C, Zhang X, Roeffaers MB, Clardy J. Small molecule perimeter defense in entomopathogenic bacteria. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 10821-10826. PMID: 22711807, PMCID: PMC3390839, DOI: 10.1073/pnas.1201160109.Peer-Reviewed Original ResearchConceptsBacterial cell surfaceConfocal fluorescence microscopyCell surfacePhysical associationHuman pathogen Vibrio choleraeInsect innate immune systemBiochemical assaysInnate immune systemPathogen Vibrio choleraeFluorescence microscopyPrecursor-directed biosynthesisE. coli cellsInsect pathogensPathway mutantsEntomopathogenic bacteriaHeterologous expressionXenorhabdus nematophilaColi cellsEscherichia coliVibrio choleraeClass of moleculesBioorthogonal probesEffective inhibitor concentrationBiosynthesisHost defense
2008
Starter unit specificity directs genome mining of polyketide synthase pathways in fungi
Crawford JM, Vagstad AL, Ehrlich KC, Townsend CA. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi. Bioorganic Chemistry 2008, 36: 16-22. PMID: 18215412, PMCID: PMC3200548, DOI: 10.1016/j.bioorg.2007.11.002.Peer-Reviewed Original ResearchConceptsHybrid metabolitesPathogenic fungus Coccidioides immitisPolyketide synthase pathwayHuman fungal pathogenSAT domainAflatoxin clusterGenome miningSynthase subunitsPolyketide synthasePKS clustersACP domainStarter unitProtein databasePolyketide synthesisFungal pathogensFunctional similarityHexanoyl-CoA.Fatty acid productsEscherichia coliSynthase pathwayFungiFungus Coccidioides immitisAspergillus speciesPathwayDomain