2023
Identification of Efflux Substrates Using a Riboswitch-Based Reporter in Pseudomonas aeruginosa
Urdaneta-Páez V, Hamchand R, Anthony K, Crawford J, Sutherland A, Kazmierczak B. Identification of Efflux Substrates Using a Riboswitch-Based Reporter in Pseudomonas aeruginosa. MSphere 2023, 8: e00069-23. PMID: 36946743, PMCID: PMC10117056, DOI: 10.1128/msphere.00069-23.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBacterial Outer Membrane ProteinsDrug Resistance, Multiple, BacterialMembrane Transport ProteinsPseudomonas aeruginosaRiboswitchConceptsLiquid chromatography-mass spectrometryCompound uptakeHigh-resolution liquid chromatography-mass spectrometryChromatography-mass spectrometryNovel antibioticsHigh-throughput screeningRational designMore rational designChemical librariesDiverse compoundsInitial hitsSelect compoundsPermeable compoundsDrug candidatesCompoundsStructural propertiesBacterial cellsPowerful methodAntifolate drugsSubstrateSpectrometrySynthesisPseudomonas aeruginosaClasses of antibioticsMembrane
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 ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAutoimmunityBiotransformationImmunologic FactorsMicePhotorhabdusResorcinolsStilbenesConceptsMethicillin-resistant Staphylococcus aureusVancomycin-resistant Enterococcus faecalisColitis mouse modelInflammatory bowel diseaseInflammatory bacteriaBowel diseaseAtopic dermatitisDietary stilbenesMouse modelDrug metabolismTapinarofStaphylococcus aureusEnterococcus faecalisMetabolism productsDisease symptomsPsoriasisDermatitisImmunomodulatorsSymptomsNrf2Disease
2018
Discovering antibiotics from the global microbiome
Lam YC, Crawford JM. Discovering antibiotics from the global microbiome. Nature Microbiology 2018, 3: 392-393. PMID: 29588534, DOI: 10.1038/s41564-018-0135-5.Peer-Reviewed Original Research
2017
A New Nucleoside Antibiotic Chokes Bacterial RNA Polymerase
Trautman EP, Crawford JM. A New Nucleoside Antibiotic Chokes Bacterial RNA Polymerase. Biochemistry 2017, 56: 4923-4924. PMID: 28885002, DOI: 10.1021/acs.biochem.7b00680.Peer-Reviewed Original Research
2016
Activating and Attenuating the Amicoumacin Antibiotics
Park HB, Perez CE, Perry EK, Crawford JM. Activating and Attenuating the Amicoumacin Antibiotics. Molecules 2016, 21: 824. PMID: 27347911, PMCID: PMC5055758, DOI: 10.3390/molecules21070824.Peer-Reviewed Original Research
2011
Dihydrophenylalanine: A Prephenate-Derived Photorhabdus luminescens Antibiotic and Intermediate in Dihydrostilbene Biosynthesis
Crawford JM, Mahlstedt SA, Malcolmson SJ, Clardy J, Walsh CT. Dihydrophenylalanine: A Prephenate-Derived Photorhabdus luminescens Antibiotic and Intermediate in Dihydrostilbene Biosynthesis. Cell Chemical Biology 2011, 18: 1102-1112. PMID: 21944749, PMCID: PMC3183431, DOI: 10.1016/j.chembiol.2011.07.009.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