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 ResearchMeSH KeywordsCell MembraneCell Surface Display TechniquesHigh-Throughput Nucleotide SequencingPeptide LibraryPseudomonas aeruginosaSingle-Domain AntibodiesVirulence FactorsConceptsBacterial 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 ResearchMeSH KeywordsAnti-Bacterial AgentsBacterial Outer Membrane ProteinsDrug Resistance, Multiple, BacterialMembrane Transport ProteinsPseudomonas aeruginosaRiboswitchConceptsLiquid 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
2020
The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung
Kazmierczak BI. The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung. Cell Host & Microbe 2020, 28: 502-504. PMID: 33031766, DOI: 10.1016/j.chom.2020.09.009.Peer-Reviewed Original ResearchHfq and sRNA 179 Inhibit Expression of the Pseudomonas aeruginosa cAMP-Vfr and Type III Secretion Regulons
Janssen KH, Corley JM, Djapgne L, Cribbs JT, Voelker D, Slusher Z, Nordell R, Regulski EE, Kazmierczak BI, McMackin EW, Yahr TL. Hfq and sRNA 179 Inhibit Expression of the Pseudomonas aeruginosa cAMP-Vfr and Type III Secretion Regulons. MBio 2020, 11: 10.1128/mbio.00363-20. PMID: 32546612, PMCID: PMC7298702, DOI: 10.1128/mbio.00363-20.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCyclic AMP Receptor ProteinCyclic AMP-Dependent Protein KinasesGene Expression Regulation, BacterialGene LibraryHost Factor 1 ProteinPromoter Regions, GeneticPseudomonas aeruginosaRegulonRNA, BacterialRNA, Small UntranslatedTranscription, GeneticType III Secretion SystemsVirulence FactorsConceptsSmall noncoding RNAsType III secretion systemSecretion systemNoncoding RNAsGene expressionTranscription factorsExpression libraryGac/Rsm systemType VI secretion systemT3SS gene expressionCAMP-responsive transcription factorRNA-binding proteinVirulence factorsGram-negative opportunistic pathogenRNA chaperonesGlobal regulatorT3SS regulonMutant lackingTarget mRNAsCritical virulence factorImportant virulence factorMRNA targetsHfqRegulonRsm systemA Screen for Antibiotic Resistance Determinants Reveals a Fitness Cost of the Flagellum in Pseudomonas aeruginosa
Rundell EA, Commodore N, Goodman AL, Kazmierczak BI. A Screen for Antibiotic Resistance Determinants Reveals a Fitness Cost of the Flagellum in Pseudomonas aeruginosa. Journal Of Bacteriology 2020, 202: 10.1128/jb.00682-19. PMID: 31871033, PMCID: PMC7043666, DOI: 10.1128/jb.00682-19.Peer-Reviewed Original ResearchConceptsFlagellar assemblyFitness advantageFitness costsCell envelopeOuter membrane barrier functionOuter membrane biogenesisUnbiased high-throughput approachOuter membrane barrierMembrane barrier functionHigh-throughput approachMembrane biogenesisGram-negative bacteriaFlagellar functionInsertion sequencingOuter membraneGene productsPresence of linezolidPresence of antibioticsAntibiotic resistance determinantsMembrane barrierAntibiotic entryFitnessEfflux pumpsGlycopeptide antibiotic vancomycinGenes
2019
Modulation of flagellar rotation in surface-attached bacteria: A pathway for rapid surface-sensing after flagellar attachment
Schniederberend M, Williams JF, Shine E, Shen C, Jain R, Emonet T, Kazmierczak BI. Modulation of flagellar rotation in surface-attached bacteria: A pathway for rapid surface-sensing after flagellar attachment. PLOS Pathogens 2019, 15: e1008149. PMID: 31682637, PMCID: PMC6855561, DOI: 10.1371/journal.ppat.1008149.Peer-Reviewed Original ResearchConceptsFlagellar rotationSurface-attached bacteriaGram-negative opportunistic pathogen Pseudomonas aeruginosaOpportunistic pathogen Pseudomonas aeruginosaSwitch complex proteinsSingle polar flagellumBiofilm formationSurface-associated behaviorsSurface-associated structuresType IV piliPathogen Pseudomonas aeruginosaGenetic screenPolar flagellumTranscriptional programsBiofilm initiationComplex proteinsMutant bacteriaFlagellar attachmentSecond messengerP. aeruginosaFlhFBacteriaFlagellaPathwayAltered behaviorIn Situ Structures of Polar and Lateral Flagella Revealed by Cryo-Electron Tomography
Zhu S, Schniederberend M, Zhitnitsky D, Jain R, Galán JE, Kazmierczak BI, Liu J. In Situ Structures of Polar and Lateral Flagella Revealed by Cryo-Electron Tomography. Journal Of Bacteriology 2019, 201: 10.1128/jb.00117-19. PMID: 31010901, PMCID: PMC6560136, DOI: 10.1128/jb.00117-19.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCryoelectron MicroscopyElectron Microscope TomographyFlagellaGene Expression Regulation, BacterialPseudomonas aeruginosaSalmonella typhimuriumConceptsCryo-electron tomographyBacterial flagellaFlagellar assemblyPolar flagellumPeritrichous flagellaSerovar TyphimuriumSpecies-specific featuresBacterial pathogensOuter membrane complexSelf-assembling nanomachineFlagellar systemFlagellar structureFlagellar numberSubtomogram averagingMembrane complexLateral flagellaStructural basisDistinct flagellaMolecular machinesFlagellaSitu structureModel systemPseudomonasTyphimuriumRange of variationShould I Stay or Should I Go? Pseudomonas Just Can’t Decide
Jain R, Kazmierczak BI. Should I Stay or Should I Go? Pseudomonas Just Can’t Decide. Cell Host & Microbe 2019, 25: 5-7. PMID: 30629919, DOI: 10.1016/j.chom.2018.12.011.Peer-Reviewed Original Research
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
Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly
Jain R, Sliusarenko O, Kazmierczak BI. Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly. PLOS Pathogens 2017, 13: e1006594. PMID: 28854278, PMCID: PMC5595344, DOI: 10.1371/journal.ppat.1006594.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCarrier ProteinsChromatography, GelCyclic GMPFimbriae, BacterialImage Processing, Computer-AssistedIntracellular Signaling Peptides and ProteinsMicroscopy, Electron, TransmissionOxidoreductasesPolymerase Chain ReactionPseudomonas aeruginosaSurface Plasmon ResonanceVirulenceVirulence FactorsConceptsT4P assemblyAssembly ATPaseTwitching motilityPoint mutant alleleBacterial cell envelopeType IVa piliGMP receptorPilus assemblyBacterial surface structuresCell envelopeFimXLocalization patternsMutant allelesSecond messengerPilBBiofilm formationATPase activityDirectional movementIntracellular levelsPilTT4PATPaseBacteriaMotilityAssemblyInflammation: 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
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 Research
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 ResearchMeSH KeywordsAnimalsInterleukin-1alphaInterleukin-1betaLungMiceMice, Inbred C57BLPseudomonas aeruginosaConceptsIL-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
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 cultures