2024
Bacterial cell surface characterization by phage display coupled to high-throughput sequencing
Grun C, Jain R, Schniederberend M, Shoemaker C, Nelson B, Kazmierczak B. Bacterial cell surface characterization by phage display coupled to high-throughput sequencing. Nature Communications 2024, 15: 7502. PMID: 39209859, PMCID: PMC11362561, DOI: 10.1038/s41467-024-51912-7.Peer-Reviewed Original ResearchConceptsBacterial cell surfaceCell surfacePhage displayP. aeruginosa virulence factorsHigh-throughput DNA sequencingHigh-throughput sequencingPhage display panningCapacity of bacteriaCamelid single-domain antibodiesVirulence factorsDNA sequencesBacterial genotypesPhageSingle-domain antibodiesPseudomonas aeruginosaHost defenseBiological informationAntimicrobial resistanceLiving cellsSequenceChronic infectionCell surface characterizationAdaptive changesCellsBacteria
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 ResearchConceptsLiquid 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
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 ResearchConceptsP. 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
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 recruitmentCheating 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
2012
The GTPase Activity of FlhF Is Dispensable for Flagellar Localization, but Not Motility, in Pseudomonas aeruginosa
Schniederberend M, Abdurachim K, Murray TS, Kazmierczak BI. The GTPase Activity of FlhF Is Dispensable for Flagellar Localization, but Not Motility, in Pseudomonas aeruginosa. Journal Of Bacteriology 2012, 195: 1051-1060. PMID: 23264582, PMCID: PMC3571332, DOI: 10.1128/jb.02013-12.Peer-Reviewed Original ResearchConceptsFlagellar functionGTPase activityOpportunistic human pathogen Pseudomonas aeruginosaHuman pathogen Pseudomonas aeruginosaSignal recognition particlePathogen Pseudomonas aeruginosaSingle-cell assaysFlhF proteinFlagellar localizationFlagellar assemblyRecognition particleAbiotic environmentProtein dimerizationFlagellar rotationNucleotide bindingFlhFPoint mutantsSurface organellesSwimming motilityBacterial motilityP. aeruginosaBacillus subtilisPseudomonas aeruginosaEnzymatic activityHydrolytic activityThe 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 Transduction
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
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
FlhF Is Required for Swimming and Swarming in Pseudomonas aeruginosa
Murray TS, Kazmierczak BI. FlhF Is Required for Swimming and Swarming in Pseudomonas aeruginosa. Journal Of Bacteriology 2006, 188: 6995-7004. PMID: 16980502, PMCID: PMC1595508, DOI: 10.1128/jb.00790-06.Peer-Reviewed Original ResearchConceptsWild-type bacteriaAssembly of flagellaRod-shaped organismExpression of flagellinFlhF proteinFlagellar assemblyFlagellar genesFlagellar poleFlhFFlagellin expressionMonotrichous bacteriaDecreased transcriptionCell surfaceBacteria resultsBacteriaLiquid mediumTranscriptionFlagellaOrganismsProteinDifferent motility patternsAberrant placementPseudomonas aeruginosaMotilityExpressionMutational 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
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
2003
Epithelial Cell Polarity Alters Rho-GTPase Responses to Pseudomonas aeruginosa
Kazmierczak BI, Mostov K, Engel JN. Epithelial Cell Polarity Alters Rho-GTPase Responses to Pseudomonas aeruginosa. Molecular Biology Of The Cell 2003, 15: 411-419. PMID: 14595106, PMCID: PMC329196, DOI: 10.1091/mbc.e03-08-0559.Peer-Reviewed Original ResearchConceptsRho family GTPasesPolarized MDCK monolayersActin polymerizationP. aeruginosa entryRho family GTPase activationMDCK monolayersCdc42-GTP levelsClostridium difficile toxin BOpportunistic human pathogenMadin-Darby canine kidney cellsActivation of RhoAEpithelial cellsDifficile toxin BCanine kidney cellsCell polarityBasolateral infectionMDCK cell monolayersGTPase activationDifferentiation stateP. aeruginosaPseudomonas aeruginosaSurface proteinsBasolateral surfaceHuman pathogensGTPases