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
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
2017
Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection
Lin CK, Kazmierczak BI. Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection. Journal Of Innate Immunity 2017, 9: 250-261. PMID: 28222444, PMCID: PMC5469373, DOI: 10.1159/000455857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesHost-Pathogen InteractionsHumansImmunity, InnateInflammasomesInflammationOpportunistic InfectionsPseudomonas aeruginosaPseudomonas InfectionsConceptsP. aeruginosa pulmonary infectionInnate immune recognitionPseudomonas aeruginosa infectionInflamed airwaysPulmonary infectionAcute infectionAdjunct therapyChronic infectionBarrier defenseAeruginosa infectionAnatomic sitesPathogen clearanceBacterial productsImmune recognitionInnate immunityInfectionHost outcomesResistant pathogensP. aeruginosa adaptationInflammationP. aeruginosaPathogen persistenceDouble-Edged SwordPseudomonas aeruginosaDefense mechanisms
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 damage
2014
A 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
2012
The Ability of Virulence Factor Expression by Pseudomonas aeruginosa to Predict Clinical Disease in Hospitalized Patients
Ledizet M, Murray TS, Puttagunta S, Slade MD, Quagliarello VJ, Kazmierczak BI. The Ability of Virulence Factor Expression by Pseudomonas aeruginosa to Predict Clinical Disease in Hospitalized Patients. PLOS ONE 2012, 7: e49578. PMID: 23152923, PMCID: PMC3495863, DOI: 10.1371/journal.pone.0049578.Peer-Reviewed Original ResearchConceptsP. aeruginosa infectionAeruginosa infectionBacterial factorsHospitalized patientsUrinary tractPositive P. aeruginosa culturesP. aeruginosaUrinary tract cathetersP. aeruginosa isolatesLogistic regression modelsPseudomonas aeruginosaProspective cohortDiabetes mellitusSubgroup analysisClinical dataTreatment decisionsClinical diseaseAeruginosa isolatesAnimal modelsPatientsClinical sitesFactor expressionInfectionHost factorsP. aeruginosa culturesThe Carbon Monoxide Releasing Molecule CORM-2 Attenuates Pseudomonas aeruginosa Biofilm Formation
Murray TS, Okegbe C, Gao Y, Kazmierczak BI, Motterlini R, Dietrich LE, Bruscia EM. The Carbon Monoxide Releasing Molecule CORM-2 Attenuates Pseudomonas aeruginosa Biofilm Formation. PLOS ONE 2012, 7: e35499. PMID: 22563385, PMCID: PMC3338523, DOI: 10.1371/journal.pone.0035499.Peer-Reviewed Original ResearchConceptsCORM-2 treatmentP. aeruginosa lung infectionP. aeruginosaAeruginosa lung infectionCORM-2Clinical P. aeruginosaMolecule CORM-2Current antimicrobial agentsChronic infectionLung infectionNew therapiesRelated infectionsNon-mucoid strainsReactive oxygen speciesInfectionNovel therapeutic propertiesTherapeutic propertiesAntimicrobial agentsAdditive effectPseudomonas aeruginosaBiofilm formationOxygen speciesTreatmentAeruginosa
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 recognitionInfectionReceptorsSwarming motility, secretion of type 3 effectors and biofilm formation phenotypes exhibited within a large cohort of Pseudomonas aeruginosa clinical isolates
Murray TS, Ledizet M, Kazmierczak BI. Swarming motility, secretion of type 3 effectors and biofilm formation phenotypes exhibited within a large cohort of Pseudomonas aeruginosa clinical isolates. Journal Of Medical Microbiology 2010, 59: 511-520. PMID: 20093376, PMCID: PMC2855384, DOI: 10.1099/jmm.0.017715-0.Peer-Reviewed Original Research
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 bacteriumDeathAeruginosaPseudomonas aeruginosa chronic colonization in cystic fibrosis patients
Murray TS, Egan M, Kazmierczak BI. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Current Opinion In Pediatrics 2007, 19: 83-88. PMID: 17224667, DOI: 10.1097/mop.0b013e3280123a5d.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBiofilmsBronchiolitisChildCystic FibrosisHumansLungMacrolidesMucusPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionVirulenceConceptsCystic fibrosis patientsChronic colonizationAcute infectionFibrosis patientsCystic fibrosisP. aeruginosaChronic pulmonary colonizationChronic pulmonary diseaseCystic fibrosis airwayHost immune systemMucoid P. aeruginosaP. aeruginosa behaviorCystic fibrosis lungPulmonary diseaseClinical benefitChronic infectionP. aeruginosa pathogenesisLeading causePulmonary colonizationNew therapiesImmune systemAggressive usePotential therapeuticsInfectionPatients
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 role
2005
An indirect enzyme-linked immunosorbent assay for rapid and quantitative assessment of Type III virulence phenotypes of Pseudomonas aeruginosa isolates
Li L, Ledizet M, Kar K, Koski RA, Kazmierczak BI. An indirect enzyme-linked immunosorbent assay for rapid and quantitative assessment of Type III virulence phenotypes of Pseudomonas aeruginosa isolates. Annals Of Clinical Microbiology And Antimicrobials 2005, 4: 22. PMID: 16375761, PMCID: PMC1360672, DOI: 10.1186/1476-0711-4-22.Peer-Reviewed Original ResearchConceptsClinical isolatesEpithelial cellsOptimal treatment strategyLarge clinical studiesP. aeruginosa type III secretion systemP. aeruginosa isolatesEnzyme-linked immunosorbent assayEnzyme-linked immunosorbentType III secretion systemSecretion phenotypeIndirect enzyme-linked immunosorbentPseudomonas aeruginosaPoor outcomeInfected patientsIndirect enzyme-linked immunosorbent assayTreatment strategiesClinical studiesClinical diseaseSevere diseaseAeruginosa isolatesELISA assaysConclusionThe availabilityImmunosorbent assayCultured epithelial cellsVirulence factors
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