2020
Dimeric Stilbene Antibiotics Target the Bacterial Cell Wall in Drug-Resistant Gram-Positive Pathogens
Goddard TN, Patel J, Park HB, Crawford JM. Dimeric Stilbene Antibiotics Target the Bacterial Cell Wall in Drug-Resistant Gram-Positive Pathogens. Biochemistry 2020, 59: 1966-1971. PMID: 32410442, PMCID: PMC10578317, DOI: 10.1021/acs.biochem.0c00213.Peer-Reviewed Original ResearchConceptsChemical complementation studiesBacterial cell wallMass spectrometry analysisLipid IILead compoundsMultidrug-resistant Gram-positive pathogensStilbene dimersCell wall precursorsSpectrometry analysisDrug-Resistant GramNew antimicrobial agentsGram-positive pathogensDimersNonlethal exposureAntibiotic targetsPositive pathogensDietary plantsAction studiesAntibiotic resistanceMode of actionAntimicrobial agentsLead dimerWall precursorsMonomersStrong activityBacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent Antibiotics
Park HB, Goddard TN, Oh J, Patel J, Wei Z, Perez CE, Mercado BQ, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford J. Bacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent Antibiotics. Angewandte Chemie International Edition 2020, 59: 7871-7880. PMID: 32097515, PMCID: PMC7200298, DOI: 10.1002/anie.201916204.Peer-Reviewed Original ResearchConceptsMethicillin-resistant Staphylococcus aureusVancomycin-resistant Enterococcus faecalisColitis mouse modelInflammatory bowel diseaseInflammatory bacteriaBowel diseaseAtopic dermatitisDietary stilbenesMouse modelDrug metabolismTapinarofStaphylococcus aureusEnterococcus faecalisMetabolism productsDisease symptomsPsoriasisDermatitisImmunomodulatorsSymptomsNrf2Disease
2017
Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis
Park HB, Sampathkumar P, Perez CE, Lee JH, Tran J, Bonanno JB, Hallem EA, Almo SC, Crawford JM. Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis. Journal Of Biological Chemistry 2017, 292: 6680-6694. PMID: 28246174, PMCID: PMC5399116, DOI: 10.1074/jbc.m116.762542.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Infective AgentsBiological ProductsCatalysisChromatography, High Pressure LiquidCrystallography, X-RayDNA Mutational AnalysisEpoxy CompoundsGene DeletionHydrogen BondingHydrophobic and Hydrophilic InteractionsImmunosuppressive AgentsMagnetic Resonance SpectroscopyMolecular ConformationMutationPhotorhabdusProtein FoldingRhabditoideaStereoisomerismStilbenesSymbiosisConceptsFood signalsInsect infection modelFAD-dependent monooxygenasesFAD prosthetic groupOrphan proteinsInsect larvaeMutualistic relationshipEpoxidase geneNematode developmentCellular detoxificationBiological roleProsthetic groupIntracellular detoxificationAnimal infection modelsInfection modelBiochemical analysisChemical degradation studiesStructural viewNematodesDetoxificationNew insightsCompound 1Major componentNew stilbeneRecovery assays
2011
Bacterial symbionts and natural products
Crawford JM, Clardy J. Bacterial symbionts and natural products. Chemical Communications 2011, 47: 7559-7566. PMID: 21594283, PMCID: PMC3174269, DOI: 10.1039/c1cc11574j.Peer-Reviewed Original Research
2010
Exploiting a Global Regulator for Small Molecule Discovery in Photorhabdus luminescens
Kontnik R, Crawford JM, Clardy J. Exploiting a Global Regulator for Small Molecule Discovery in Photorhabdus luminescens. ACS Chemical Biology 2010, 5: 659-665. PMID: 20524642, PMCID: PMC2912427, DOI: 10.1021/cb100117k.Peer-Reviewed Original ResearchConceptsGlobal transcriptional regulatorSmall moleculesSecondary metabolite productionGenes/lociTight regulatory controlUseful biological probesSmall molecule discoverySuch small moleculesGlobal regulatorBacterial genomesFunctional diversityInsect larvaeTranscriptional regulatorsTranscriptional repressorComplex symbiosisNematode wormsMetabolite productionMolecule discoveryPhotorhabdusMutantsDramatic upregulationSymbiosisRegulatory controlRemarkable rangeRegulator