2021
A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosa
Lin CK, Lee DSW, McKeithen-Mead S, Emonet T, Kazmierczak B. A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosa. MBio 2021, 12: 10.1128/mbio.00831-21. PMID: 34154400, PMCID: PMC8262847, DOI: 10.1128/mbio.00831-21.Peer-Reviewed Original ResearchConceptsType 3 secretion systemSecretion systemT3SS expressionVirulence traitsSpecific virulence traitsHuman disease severityComplex nanomachinesT3SS genesP. aeruginosa cellsReproductive fitnessIsogenic cellsHeterogeneous expressionCell envelopeT3SS effectorsMotility organellesReservoir of cellsCritical virulence traitsGene expressionRegulatory mechanismsSubpopulation of cellsGram-negative pathogensFluorescent reportersDivision timeP. aeruginosaPseudomonas aeruginosa
2020
Global chemical effects of the microbiome include new bile-acid conjugations
Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 2020, 579: 123-129. PMID: 32103176, PMCID: PMC7252668, DOI: 10.1038/s41586-020-2047-9.Peer-Reviewed Original ResearchConceptsChemical interactionChemistryBile acid synthesis genesChemical effectsInflammatory bowel diseaseBile acid conjugatesCompoundsHost bile acidsMolecular familiesBile acid conjugationBowel diseaseGut diseasesMicrobiome dysbiosisConjugationAcidFree miceAmino acid conjugationBile acidsCystic fibrosisX receptorAcid conjugationReduced expressionFurther studiesDiseaseMice
2018
Host suppression of quorum sensing during catheter-associated urinary tract infections
Cole SJ, Hall CL, Schniederberend M, Farrow III JM, Goodson JR, Pesci EC, Kazmierczak BI, Lee VT. Host suppression of quorum sensing during catheter-associated urinary tract infections. Nature Communications 2018, 9: 4436. PMID: 30361690, PMCID: PMC6202348, DOI: 10.1038/s41467-018-06882-y.Peer-Reviewed Original ResearchConceptsCatheter-associated urinary tract infectionsUrinary tract infectionTract infectionsChronic bacterial infectionP. aeruginosaAntibiotic therapyUrinary tractDevice-associated biofilmsMurine modelHost immunityClinical isolatesBacterial infectionsInfectionPseudomonas aeruginosaUrineAeruginosaTherapyRegulated genesImmunityTract
2016
Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia
Marion CR, Wang J, Sharma L, Losier A, Lui W, Andrews N, Elias JA, Kazmierczak BI, Roy CR, Dela Cruz CS. Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia. Infection And Immunity 2016, 84: 2094-2104. PMID: 27141083, PMCID: PMC4936356, DOI: 10.1128/iai.00055-16.Peer-Reviewed Original ResearchConceptsBone marrow-derived macrophagesTumor necrosis factor alphaExcessive IL-1β productionNecrosis factor alphaIL-1β productionWT miceAeruginosa pneumoniaFactor alphaChitinase 3Lung parenchymal damageHospital-acquired pneumoniaIL-13 receptor α2Pseudomonas aeruginosa pneumoniaP. aeruginosa pneumoniaDecreased survival timeStreptococcus pneumoniae infectionHost inflammatory responseP. aeruginosa infectionInterleukin-1β productionMarrow-derived macrophagesHost tissue damageP. aeruginosaHost tolerancePneumoniae infectionParenchymal damageNAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo
Rauch I, Tenthorey JL, Nichols RD, Moussawi K, Kang JJ, Kang C, Kazmierczak BI, Vance RE. NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. Journal Of Experimental Medicine 2016, 213: 657-665. PMID: 27045008, PMCID: PMC4854734, DOI: 10.1084/jem.20151809.Peer-Reviewed Original ResearchConceptsSpecific bacterial proteinsNAIP proteinsNeedle proteinBacterial proteinsGenetic evidenceSpecific bacterial ligandsBacterial ligandsBacterial type III secretion systemInner rod proteinType III secretion systemT3SS needle proteinStrong biochemical evidenceCytosolic flagellinFlagellin detectionRod proteinsSecretion systemDetection of flagellinCRISPR/Diverse functionsCytosolic detectionNAIP1ProteinBiochemical evidenceNAIPsFlagellin
2015
Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence
Kazmierczak BI, Schniederberend M, Jain R. Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence. Current Opinion In Microbiology 2015, 28: 78-82. PMID: 26476804, PMCID: PMC4688086, DOI: 10.1016/j.mib.2015.07.017.Peer-Reviewed Original ResearchCompartment-Specific and Sequential Role of MyD88 and CARD9 in Chemokine Induction and Innate Defense during Respiratory Fungal Infection
Jhingran A, Kasahara S, Shepardson KM, Junecko BA, Heung LJ, Kumasaka DK, Knoblaugh SE, Lin X, Kazmierczak BI, Reinhart TA, Cramer RA, Hohl TM. Compartment-Specific and Sequential Role of MyD88 and CARD9 in Chemokine Induction and Innate Defense during Respiratory Fungal Infection. PLOS Pathogens 2015, 11: e1004589. PMID: 25621893, PMCID: PMC4306481, DOI: 10.1371/journal.ppat.1004589.Peer-Reviewed Original ResearchConceptsRespiratory fungal infectionsDistinct signal transduction pathwaysSignal transduction pathwaysNeutrophil recruitmentChemokine inductionGenetic deletionFungal infectionsFungal clearanceCellular compartmentsTransduction pathwaysC-type lectinProtein triggersLung epithelial cellsNeutrophil-dependent host defenseInterleukin-1 receptorReceptor signalsConidial uptakeLung neutrophil recruitmentLung-infiltrating neutrophilsNeutrophil chemokines CXCL1Sequential rolesMyD88-deficient miceHematopoietic compartmentProtein knockout miceMajor cellular source
2014
Distinct Contributions of Interleukin-1α (IL-1α) and IL-1β to Innate Immune Recognition of Pseudomonas aeruginosa in the Lung
Al Moussawi K, Kazmierczak BI. Distinct Contributions of Interleukin-1α (IL-1α) and IL-1β to Innate Immune Recognition of Pseudomonas aeruginosa in the Lung. Infection And Immunity 2014, 82: 4204-4211. PMID: 25069982, PMCID: PMC4187872, DOI: 10.1128/iai.02218-14.Peer-Reviewed Original ResearchConceptsIL-1βIL-1αImmune responseCaspase-1Deficient miceExtracellular Toll-like receptorsNLRC4 inflammasomeStrong innate immune responseIL-1β signalRecruitment of neutrophilsToll-like receptorsInnate immune recognitionIL-1 receptorP. aeruginosa isolatesInnate immune responseP. aeruginosa infectionSite of infectionIL-1α secretionT3SS effectorsWild-type animalsNegative bacterial isolatesPseudomonas aeruginosaNeutrophilic responseAcute infectionNeutrophil recruitmentA Conservative Amino Acid Mutation in the Master Regulator FleQ Renders Pseudomonas aeruginosa Aflagellate
Jain R, Kazmierczak BI. A Conservative Amino Acid Mutation in the Master Regulator FleQ Renders Pseudomonas aeruginosa Aflagellate. PLOS ONE 2014, 9: e97439. PMID: 24827992, PMCID: PMC4020848, DOI: 10.1371/journal.pone.0097439.Peer-Reviewed Original ResearchConceptsMurine pulmonary infectionIL-1 signalPresence of mutationsPulmonary infectionAcute infectionBacterial clearanceHost responseBacterial infectionsClinical strainsInfectionSystem expressionAmino acid changesAmino acid mutationsSingle amino acid changeStrain PA103ClearanceAmino acid substitutionsPseudomonas aeruginosa pathogenesisPathogen recognitionAcid changesPA103Negative correlationMotilityAcid mutationsConservative amino acid substitutionsCheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection
Czechowska K, McKeithen-Mead S, Moussawi K, Kazmierczak BI. Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 7801-7806. PMID: 24821799, PMCID: PMC4040582, DOI: 10.1073/pnas.1400782111.Peer-Reviewed Original ResearchConceptsT3SS-inducing conditionsOpportunistic pathogen Pseudomonas aeruginosaType 3 secretion systemPathogen Pseudomonas aeruginosaWT P. aeruginosaPositive bacteriaFitness advantageDefective mutantsRelative fitnessSecretion systemBacterial virulenceSelective advantageMyD88 knockout miceNeutrophil-depleted animalsVitro growth rateMutantsInnate immune cellsPseudomonas aeruginosaP. aeruginosa infectionCompetition experimentsAcute pneumonia modelBacteriaFitnessPulmonary infectionImmunocompetent hosts
2013
Flagellar Motility Is a Key Determinant of the Magnitude of the Inflammasome Response to Pseudomonas aeruginosa
Patankar YR, Lovewell RR, Poynter ME, Jyot J, Kazmierczak BI, Berwin B. Flagellar Motility Is a Key Determinant of the Magnitude of the Inflammasome Response to Pseudomonas aeruginosa. Infection And Immunity 2013, 81: 2043-2052. PMID: 23529619, PMCID: PMC3676033, DOI: 10.1128/iai.00054-13.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCaspase 1Cell DeathCytoskeletal ProteinsDendritic CellsFlagellaGene Expression RegulationInflammasomesInterleukin-1betaMacrophages, PeritonealMiceMice, Inbred C57BLMice, KnockoutMovementPhagocytosisPseudomonas aeruginosaPseudomonas InfectionsConceptsBacterial motilityFlagellar motilityBacterial flagellar motilityInnate immune systemWild-type P. aeruginosaInflammasome activationP. aeruginosaFlagellar expressionIngest bacteriaBone marrow-derived dendritic cellsImmune systemNLRC4 inflammasome activationBacterial associationsCaspase-1 activationBacterial interactionsMarrow-derived dendritic cellsChronic Pseudomonas aeruginosa infectionIL-1β levelsCell surfacePseudomonas aeruginosa infectionIL-1β productionInflammasome responseMotilityDendritic cellsAeruginosa infection
2011
Innate immune responses to Pseudomonas aeruginosa infection
Lavoie EG, Wangdi T, Kazmierczak BI. Innate immune responses to Pseudomonas aeruginosa infection. Microbes And Infection 2011, 13: 1133-1145. PMID: 21839853, PMCID: PMC3221798, DOI: 10.1016/j.micinf.2011.07.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsComplement System ProteinsCytokinesDendritic CellsHumansImmunity, InnateInflammasomesLipopolysaccharidesLungLymphocytesMacrophages, AlveolarMiceMice, KnockoutNeutrophilsPneumoniaPseudomonas aeruginosaPseudomonas InfectionsReceptors, Pattern RecognitionSignal TransductionAirway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway
Mijares LA, Wangdi T, Sokol C, Homer R, Medzhitov R, Kazmierczak BI. Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway. The Journal Of Immunology 2011, 186: 7080-7088. PMID: 21572023, PMCID: PMC3110630, DOI: 10.4049/jimmunol.1003687.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseMyD88-dependent innate immune responsesIL-1-dependent pathwayBone marrow chimeric miceProtective innate immune responseP. aeruginosaNovel transgenic mouse modelVentilator-associated pneumoniaIL-1R signalingTransgenic mouse modelP. aeruginosa infectionEpithelial cell responsesRadio-resistant cellsIntranasal infectionMyD88 expressionMultiple TLR pathwaysMyD88 functionAeruginosa infectionMouse modelTLR pathwayMurine infectionChimeric miceCell responsesInfection
2010
In Vivo Discrimination of Type 3 Secretion System-Positive and -Negative Pseudomonas aeruginosa via a Caspase-1-Dependent Pathway
Wangdi T, Mijares LA, Kazmierczak BI. In Vivo Discrimination of Type 3 Secretion System-Positive and -Negative Pseudomonas aeruginosa via a Caspase-1-Dependent Pathway. Infection And Immunity 2010, 78: 4744-4753. PMID: 20823203, PMCID: PMC2976309, DOI: 10.1128/iai.00744-10.Peer-Reviewed Original ResearchConceptsType 3 secretion systemSecretion systemInnate immune systemCaspase-1-dependent pathwayImmune systemBone marrow-derived cellsInterleukin-1 receptorPseudomonas aeruginosaMarrow-derived cellsMolecular patternsToll-like receptorsRapid inflammatory responseNegative bacteriaCaspase-1 activityPotential pathogensBacteriaMicrobesNegative Pseudomonas aeruginosaPulmonary infectionCaspase-1Inflammatory responseMutantsRapid recognitionInfectionReceptors
2009
Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection
Lan L, Murray TS, Kazmierczak BI, He C. Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection. Molecular Microbiology 2009, 75: 76-91. PMID: 19943895, PMCID: PMC2881571, DOI: 10.1111/j.1365-2958.2009.06955.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAnti-Bacterial AgentsBeta-Lactam ResistanceBeta-LactamsFemaleGene DeletionGene Expression Regulation, BacterialGlutathione PeroxidaseHydrogen PeroxideMiceMice, Inbred C57BLModels, BiologicalMutagenesis, Site-DirectedOxidative StressPigments, BiologicalPneumoniaPseudomonas aeruginosaPseudomonas InfectionsQuorum SensingRepressor ProteinsSignal TransductionStress, PhysiologicalTyrosineVirulenceConceptsOxidative stress sensingCys-24Stress sensingPigment productionNull mutant strainOxidative stressSerine substitution mutantsGlobal regulatorPromoter DNASubstitution mutantsAdditional genesInside hostsQuorum sensingCys residuesMutant strainConstitutive expressionMultiple pathwaysRegulatory effectsBeta-lactam resistanceGenesSignificant inductionRegulatorTyrosine metabolismOSPRP. aeruginosa
2007
Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome
Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. Journal Of Experimental Medicine 2007, 204: 3235-3245. PMID: 18070936, PMCID: PMC2150987, DOI: 10.1084/jem.20071239.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseP. aeruginosaCaspase-1Proinflammatory cytokine productionProinflammatory cytokines interleukinInfection of macrophagesCell deathHost cellsCapase-1Pseudomonas aeruginosaOpportunistic infectionsCytokine productionCytokines interleukinInflammatory responseImmune recognitionNLRC4 inflammasomeEffector moleculesType III secretion systemInfectionIPAFMacrophagesGram-negative bacteriumDeathAeruginosa
2006
Mutational Analysis of RetS, an Unusual Sensor Kinase-Response Regulator Hybrid Required for Pseudomonas aeruginosa Virulence
Laskowski MA, Kazmierczak BI. Mutational Analysis of RetS, an Unusual Sensor Kinase-Response Regulator Hybrid Required for Pseudomonas aeruginosa Virulence. Infection And Immunity 2006, 74: 4462-4473. PMID: 16861632, PMCID: PMC1539586, DOI: 10.1128/iai.00575-06.Peer-Reviewed Original ResearchConceptsType III secretion system proteinsSignal transduction domainsSecretion system proteinsUpregulation of genesPeriplasmic domainSensor kinaseReceiver domainTransmembrane domainRegulator proteinTransduction domainMutational analysisSignaling roleSystem proteinsReciprocal regulationPseudomonas aeruginosaRET activityBiofilm formationVirulence factorsOpportunistic pathogenT3SSProteinRET alleleRETP. aeruginosaKey roleAnalysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa
Kazmierczak BI, Lebron MB, Murray TS. Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. Molecular Microbiology 2006, 60: 1026-1043. PMID: 16677312, PMCID: PMC3609419, DOI: 10.1111/j.1365-2958.2006.05156.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell MovementCyclic GMPEscherichia coli ProteinsFemaleFimbriae, BacterialHeLa CellsHumansMiceMice, Inbred C57BLPhosphoric Diester HydrolasesPhosphorus-Oxygen LyasesPneumonia, BacterialPoint MutationProtein Structure, TertiaryPseudomonas aeruginosaSequence DeletionVirulenceConceptsEAL domainBacterial poleGGDEF-EAL proteinsCyclic dimeric guanosine monophosphateDiguanylate cyclase activityPolar surface structuresType IV piliWild-type strainGGDEF domainDiguanylate cyclasesREC domainLocalization signalPilus assemblyGGDEFNon-polar sitesFimXSurface piliPseudomonas aeruginosaPhosphodiesterase activityBiofilm formationProteinMutantsPiliMotilityDomain
2004
A novel sensor kinase–response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa
Laskowski MA, Osborn E, Kazmierczak BI. A novel sensor kinase–response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa. Molecular Microbiology 2004, 54: 1090-1103. PMID: 15522089, PMCID: PMC3650721, DOI: 10.1111/j.1365-2958.2004.04331.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBase SequenceCalciumFemaleGene Expression Regulation, BacterialHistidine KinaseMiceMice, Inbred C57BLProtein KinasesProtein Structure, TertiaryPseudomonas aeruginosaPseudomonas InfectionsRecombinant Fusion ProteinsSignal TransductionTrans-ActivatorsTranscription, GeneticConceptsType III secretion systemTwo-component signaling proteinsCalcium limitationResponse regulator domainType III effectorsBasal transcription rateWild-type parentNorthern blot analysisRegulator domainHistidine kinasePeriplasmic domainTranscriptional activatorEukaryotic cellsTTSS effectorsTranscriptional fusionsTransmembrane domainEnvironmental signalsSignaling proteinsSecretion systemSensor proteinsTTSS genesTranscription rateOperonPseudomonas aeruginosaEffector production
2000
The Arginine Finger Domain of ExoT Contributes to Actin Cytoskeleton Disruption and Inhibition of Internalization ofPseudomonas aeruginosa by Epithelial Cells and Macrophages
Garrity-Ryan L, Kazmierczak B, Kowal R, Comolli J, Hauser A, Engel J. The Arginine Finger Domain of ExoT Contributes to Actin Cytoskeleton Disruption and Inhibition of Internalization ofPseudomonas aeruginosa by Epithelial Cells and Macrophages. Infection And Immunity 2000, 68: 7100-7113. PMID: 11083836, PMCID: PMC97821, DOI: 10.1128/iai.68.12.7100-7113.2000.Peer-Reviewed Original ResearchConceptsEpithelial cellsImportant nosocomial pathogenType III secretion systemHost cellsMacrophage-like cellsAcute pneumoniaMouse modelNosocomial pathogenOfPseudomonas aeruginosaType IIIJ774.1 macrophage-like cellsSecretion systemStrain PA103ExoTPseudomonas aeruginosaCellsCytoskeleton disruptionNegative regulatorPA103Reduced colonizationActin cytoskeleton disruptionPrevious studiesAeruginosaPneumoniaVirulence