2024
Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?
Gallagher E, Conlin P, Kazmierczak B, Vyas J, Ajijola O, Kontos C, Baiocchi R, Rhee K, Hu P, Isales C, Williams C, Rockey D. Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine? JCI Insight 2024, 9: e178214. PMID: 38775155, PMCID: PMC11141926, DOI: 10.1172/jci.insight.178214.Peer-Reviewed Original ResearchConceptsMedical school graduatesCareer development awardsInternal medicine residency graduatesResidency graduatesRetention of physician-scientistsInternal medicinePostgraduate trainingPhysician-scientistsSchool graduatesK awardsK awardeesMD-PhD graduatesPatient careComplete trainingTraining durationMedian timeMedical knowledgeDevelopment AwardNIH RePORTERTrainingIK2GraduatesAwardeesMedicineCare
2014
Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation
Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M, Overton J, Meffre E, Khokha MK, Huttner AJ, West B, Podoltsev NA, Boggon TJ, Kazmierczak BI, Lifton RP. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nature Genetics 2014, 46: 1135-1139. PMID: 25217960, PMCID: PMC4177367, DOI: 10.1038/ng.3066.Peer-Reviewed Original ResearchA 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 substitutions
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 cultures
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
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