2022
Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 2022, 378: eabm3233. PMID: 36302024, PMCID: PMC9993714, DOI: 10.1126/science.abm3233.Peer-Reviewed Original ResearchConceptsColorectal cancerInflammatory bowel disease patientsBowel disease patientsInflammatory bowel diseaseIndigenous gut microbesBowel diseaseDisease patientsCommensal microbiotaDNA damageColon tumorigenesisElicit DNA damageGut microbesGenotoxic metabolitesGut commensalsMorganella morganiiPatientsGenotoxic chemicalsDiseaseMicrobiotaMetabolitesGenotoxicityCancerMiceFull spectrumDamageLACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages
Wei Z, Oh J, Flavell RA, Crawford JM. LACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages. Nature 2022, 609: 348-353. PMID: 35978195, PMCID: PMC9813773, DOI: 10.1038/s41586-022-05111-3.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseWild-type activityCentral regulatory roleMammalian immune systemBone marrow-derived macrophagesInflammatory macrophagesBiochemical functionsBowel diseaseSignaling outcomesMarrow-derived macrophagesPattern recognition receptorsInflammatory diseasesBiochemical roleRegulatory roleMechanistic connectionUnidentified pathwaySalmonella enterica TyphimuriumNitric oxide synthaseRecognition receptorsHost damageHuman inflammatory diseasesMultiple inflammatory diseasesEnterica TyphimuriumOrnithine decarboxylaseLACC1RNA m6A demethylase ALKBH5 regulates the development of γδ T cells
Ding C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, Oh J, Crawford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W, Flavell RA, Li HB. RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203318119. PMID: 35939687, PMCID: PMC9388086, DOI: 10.1073/pnas.2203318119.Peer-Reviewed Original ResearchConceptsDemethylase ALKBH5Messenger RNAΓδ T cellsΓδ T cell biologyCommon posttranscriptional modificationΓδ T cell developmentT cell biologyT cell developmentCell precursorsT cell precursorsMammalian cellsRNA modificationsPosttranscriptional modificationsTissue homeostasisCell biologyT cellsTarget genesCheckpoint roleCell developmentM6A demethylase ALKBH5ALKBH5Γδ T-cell originΓδ T cell repertoireCell populationsEarly development
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 modelMetabolitesBacterial 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
2019
Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
Yang J, Schleicher TR, Dong Y, Park HB, Lan J, Cresswell P, Crawford J, Dimopoulos G, Fikrig E. Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection. Journal Of Experimental Medicine 2019, 217: e20190682. PMID: 31658986, PMCID: PMC7037243, DOI: 10.1084/jem.20190682.Peer-Reviewed Original ResearchConceptsMutant mosquitoesOvarian developmentThioester-containing protein 1Rodent Plasmodium speciesMajor yolk proteinInducible lysosomal thiol reductaseAbility of sporozoitesExpression of vitellogeninLysosomal thiol reductaseAnopheles gambiae mosquitoesPlasmodium infectionMosquito immunityProtein 9Yolk proteinsThiol reductaseVertebrate hostsTraverse cellsMosquito factorsGambiae mosquitoesProtein 1Plasmodium speciesAnophelesMosquitoesMosaic mutationsParasite killingA 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
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 ResearchAcyl Histidines: New N‐Acyl Amides from Legionella pneumophila
Tørring T, Shames SR, Cho W, Roy CR, Crawford JM. Acyl Histidines: New N‐Acyl Amides from Legionella pneumophila. ChemBioChem 2017, 18: 638-646. PMID: 28116768, PMCID: PMC5546091, DOI: 10.1002/cbic.201600618.Peer-Reviewed Original ResearchConceptsBiosynthetic gene clusterOrphan biosynthetic gene clustersPathogen-insect interactionsAmino acid-derived metabolitesLegionella pneumophilaOrphan pathwaysBiosynthetic genesVariety of protozoanGene clusterN-acyl amidesMolecular networkingHuman macrophagesDistinct groupsPneumophilaCausative agentPathwayMetabolitesHistidine metabolitesNew N-acylGenesLegionnaires' diseaseAmoebaeProtozoaMacrophagesPathogens