2020
Making and Breaking Leupeptin Protease Inhibitors in Pathogenic Gammaproteobacteria
Li J, Oh J, Kienesberger S, Kim N, Clarke D, Zechner E, Crawford J. Making and Breaking Leupeptin Protease Inhibitors in Pathogenic Gammaproteobacteria. Angewandte Chemie 2020, 132: 18028-18036. DOI: 10.1002/ange.202005506.Peer-Reviewed Original ResearchBacterial small moleculesTripeptide aldehyde protease inhibitorsHeterologous expression analysisProtease inhibitorsPhotorhabdus speciesColonization phenotypesHypothetical proteinsNematode hostsPathogenic GammaproteobacteriaExpression analysisBacterial productionAccessory enzymesGenetic distributionProteolytic degradationSmall moleculesEnzymeLeupeptinKlebsiella oxytocaInhibitorsLigasesXenorhabdusGammaproteobacteriaPhotorhabdusBiosynthesisSpeciesMaking and Breaking Leupeptin Protease Inhibitors in Pathogenic Gammaproteobacteria
Li J, Oh J, Kienesberger S, Kim NY, Clarke DJ, Zechner EL, Crawford J. Making and Breaking Leupeptin Protease Inhibitors in Pathogenic Gammaproteobacteria. Angewandte Chemie International Edition 2020, 59: 17872-17880. PMID: 32609431, DOI: 10.1002/anie.202005506.Peer-Reviewed Original ResearchConceptsBacterial small moleculesTripeptide aldehyde protease inhibitorsHeterologous expression analysisProtease inhibitorsColonization phenotypesPhotorhabdus speciesHypothetical proteinsNematode hostsPathogenic GammaproteobacteriaExpression analysisBacterial productionAccessory enzymesGenetic distributionProteolytic degradationSmall moleculesEnzymeLeupeptinKlebsiella oxytocaInhibitorsGammaproteobacteriaLigasesXenorhabdusPhotorhabdusBiosynthesisSpecies
2016
Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens
Park HB, Crawford JM. Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens. The Journal Of Antibiotics 2016, 69: 616-621. PMID: 27353165, PMCID: PMC5003743, DOI: 10.1038/ja.2016.79.Peer-Reviewed Original ResearchConceptsSpecialized metabolitesNew specialized metabolitesMutualistic associationAmino acid levelsInsect pathogenesisInsect preyGalleria mellonella larvaePhotorhabdus genusP. luminescensPhenotypic variationFamilies HeterorhabditidaeNematode developmentEntomopathogenic bacteriumProtease inhibitory activityFree amino acid levelsRich mediumAmino acidsMellonella larvaePhenotypic variantsMarfey's analysisPhotorhabdusCirculatory fluidCulture extractsMetabolitesHeterorhabditidae
2012
A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States
Somvanshi VS, Sloup RE, Crawford JM, Martin AR, Heidt AJ, Kim KS, Clardy J, Ciche TA. A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States. Science 2012, 337: 88-93. PMID: 22767929, PMCID: PMC4006969, DOI: 10.1126/science.1216641.Peer-Reviewed Original ResearchConceptsNematode intestinePromoter inversionVariable life historiesM-form cellsInsect infectionHost nematodesLife historyMicrobial populationsSecondary metabolitesAntibiotic toleranceIndividual cellsNematodesPhotorhabdusM formJuvenile offspringCellsPathogenic variantsFirst cellsDistinct formsMutualistsMutualismVariantsInsectsAvirulenceSmall cell variant
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 rangeRegulatorRegulating 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