2023
Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2
Murphy T, Kirkham C, D’Mello A, Sethi S, Pettigrew M, Tettelin H. Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2. MBio 2023, 14: e00140-23. PMID: 36927061, PMCID: PMC10127715, DOI: 10.1128/mbio.00140-23.Peer-Reviewed Original ResearchMeSH KeywordsAdhesins, BacterialAdultHaemophilus InfectionsHaemophilus influenzaeHumansInflammationPulmonary Disease, Chronic ObstructiveRespiratory SystemConceptsChronic obstructive pulmonary diseaseNontypeable Haemophilus influenzaeObstructive pulmonary diseaseRespiratory epithelial cellsHuman airwaysHaemophilus influenzaeAirway inflammationLung functionMechanisms of persistencePulmonary diseaseEpithelial cellsNovel interventionsChronic lower airway infectionsProgressive lossAirways of adultsLower airway infectionHuman respiratory epithelial cellsCommon debilitating disorderStrains of NTHiNTHi infectionAirway infectionLower airwaysCommon causeSequential isolatesSerial isolates
2019
Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions
Atack JM, Murphy TF, Pettigrew MM, Seib KL, Jennings MP. Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions. Scientific Reports 2019, 9: 15963. PMID: 31685916, PMCID: PMC6828955, DOI: 10.1038/s41598-019-52429-6.Peer-Reviewed Original ResearchMeSH KeywordsAllelesDNA MethylationGene Expression Regulation, BacterialGenotypeHaemophilus InfectionsHaemophilus influenzaeHumansPeriplasmic Binding ProteinsPulmonary Disease, Chronic ObstructiveSequence Analysis, DNAConceptsNon-typeable Haemophilus influenzaeChronic obstructive pulmonary diseaseObstructive pulmonary diseaseMiddle ear infectionPulmonary diseaseEar infectionsNTHi strainsHaemophilus influenzaeExacerbation of COPDCOPDMiddle earPatientsAllele distributionInfectionInfluenzaeBacterial pathogensDiseaseMultiple allelic variantsAllelic variantsGene expressionAllelesEpigenetic mechanismsLarge panelExacerbationExpressionDiscovery and Contribution of Nontypeable Haemophilus influenzae NTHI1441 to Human Respiratory Epithelial Cell Invasion
Ahearn C, Kirkham C, Chaves L, Kong Y, Pettigrew M, Murphy T. Discovery and Contribution of Nontypeable Haemophilus influenzae NTHI1441 to Human Respiratory Epithelial Cell Invasion. Infection And Immunity 2019, 87: 10.1128/iai.00462-19. PMID: 31427451, PMCID: PMC6803334, DOI: 10.1128/iai.00462-19.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseRespiratory epithelial cellsEnzyme-linked immunosorbent assayEpithelial cellsAirways of adultsObstructive pulmonary diseaseCell invasionHuman respiratory epithelial cellsNontypeable Haemophilus influenzaeCell enzyme-linked immunosorbent assayAlveolar epithelial cellsAcute exacerbationLower airwaysPulmonary diseaseSerum IgGNTHi strainsTherapeutic interventionsHaemophilus influenzaeHuman bronchialSurface-exposed epitopesEpithelial cell invasionIsogenic knockout mutantsNTHiImmunosorbent assayIntracellular survival
2018
Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin
Murphy TF, Brauer AL, Pettigrew MM, LaFontaine ER, Tettelin H. Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin. The Journal Of Infectious Diseases 2018, 219: 1448-1455. PMID: 30496439, PMCID: PMC6467191, DOI: 10.1093/infdis/jiy680.Peer-Reviewed Original ResearchMeSH KeywordsAdhesins, BacterialAdultBacterial AdhesionGene ExpressionHumansMoraxella catarrhalisMoraxellaceae InfectionsPhenotypePulmonary Disease, Chronic ObstructiveRespiratory SystemVirulence FactorsConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseM. catarrhalisPulmonary diseaseMoraxella catarrhalisPersistent strainsDuration of persistenceHuman airwaysCatarrhalisCessation of expressionAirwayMajor pathogenPatientsBacterial pathogensDiseaseVirulence-associated phenotypesAdultsCollected strainsMost strainsExpressionHuman cellsPathogensPathogenesisPersistenceMonthsChanges in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease
Gallo MC, Kirkham C, Eng S, Bebawee RS, Kong Y, Pettigrew MM, Tettelin H, Murphy TF. Changes in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease. Infection And Immunity 2018, 86: 10.1128/iai.00313-18. PMID: 29760213, PMCID: PMC6056860, DOI: 10.1128/iai.00313-18.Peer-Reviewed Original ResearchMeSH KeywordsGene ExpressionHaemophilus InfectionsHaemophilus influenzaeHumansLongitudinal StudiesMutationNew YorkProspective StudiesPulmonary Disease, Chronic ObstructiveSerine EndopeptidasesConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseasePersistent infectionPulmonary diseaseIgA proteaseProtease expressionNontypeable Haemophilus influenzaeAcute exacerbationLower airwaysRespiratory tractNTHi strainsHaemophilus influenzaeInfectionNTHiNatural infectionHuman pathobiontAltered expressionPatientsDiseasePersistent strainsExpressionCritical roleExacerbationAirwayInitial acquisitionHaemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease
Pettigrew MM, Ahearn CP, Gent JF, Kong Y, Gallo MC, Munro JB, D’Mello A, Sethi S, Tettelin H, Murphy TF. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e3256-e3265. PMID: 29555745, PMCID: PMC5889651, DOI: 10.1073/pnas.1719654115.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceEvolution, MolecularGenome, ViralHaemophilus InfectionsHaemophilus influenzaeHumansMutationPhylogenyProspective StudiesPulmonary Disease, Chronic ObstructiveRespiratory SystemViral VaccinesVirulenceConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCandidate vaccine antigensHuman airwaysPulmonary diseaseVaccine antigensRespiratory tract pathogensHuman respiratory tractProspective studyTract pathogensNTHi isolatesRespiratory tractAnimal modelsVaccine developmentHuman infectionsAirwayNTHiSurface moleculesAmino acid sequence changesWhole-genome sequencingAntigenBacterial pathogensDiseaseSubset of strainsVirulence functionsAzithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease
Tsuji BT, Fisher J, Boadi-Yeboah R, Holden PN, Sethi S, Pettigrew MM, Murphy TF. Azithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease. Antimicrobial Agents And Chemotherapy 2018, 62: 10.1128/aac.01995-17. PMID: 29180527, PMCID: PMC5786777, DOI: 10.1128/aac.01995-17.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsAzithromycinHaemophilus InfectionsHaemophilus influenzaeHumansPulmonary Disease, Chronic ObstructiveRespiratory SystemConceptsChronic obstructive pulmonary disease patientsObstructive pulmonary disease patientsChronic obstructive pulmonary diseaseHollow-fiber infection modelStrains of NTHiPulmonary disease patientsObstructive pulmonary diseasePulmonary diseaseConcentration-dependent activityDisease patientsPharmacodynamic profilePharmacodynamic responseSame patientHaemophilus influenzaeInfection modelPatientsAzithromycinPersistent strainsDaysAirwayNTHiPharmacodynamicsInfluenzaeDiseaseHaemophilus
2017
Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease
Murphy TF, Kirkham C, Gallo MC, Yang Y, Wilding GE, Pettigrew MM. Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease. The Journal Of Infectious Diseases 2017, 216: 1295-1303. PMID: 28968876, PMCID: PMC5853902, DOI: 10.1093/infdis/jix471.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseNontypeable Haemophilus influenzaeObstructive pulmonary diseaseExpression of IgARespiratory epithelial cellsLysosomal-associated membrane protein 1Pulmonary diseaseEpithelial cellsIntracellular survivalHaemophilus influenzaeHuman respiratory epithelial cellsPathogenesis of infectionHuman respiratory tractIgA proteasePassage of strainsMembrane protein 1Host cellsProtease expressionNTHi infectionNTHi isolatesRespiratory tractHost epithelial cellsIgAIntracellular persistenceReduced survival
2016
Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease
Pettigrew MM, Tsuji BT, Gent JF, Kong Y, Holden PN, Sethi S, Murphy TF. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease. Antimicrobial Agents And Chemotherapy 2016, 60: 4151-4158. PMID: 27139476, PMCID: PMC4914697, DOI: 10.1128/aac.00301-16.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsCiprofloxacinFluoroquinolonesHaemophilus influenzaeLevofloxacinMacrolidesMicrobial Sensitivity TestsMoxifloxacinPulmonary Disease, Chronic ObstructiveConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseH. influenzae isolatesH. influenzaePulmonary diseaseFluoroquinolone administrationInfluenzae isolatesDevelopment of resistanceHaemophilus influenzaeEradication of carriageEffects of macrolidesQuinolone resistance-determining regionsMICs of antibioticsEffects of fluoroquinolonesResistance-determining regionMacrolide administrationCOPD patientsEffects of antibioticsAzithromycin MICsAntibiotic useSusceptibility breakpointsAntibiotic susceptibilityMacrolide susceptibilityInfluenzaeAdministration
2015
Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease
Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease. The Journal Of Infectious Diseases 2015, 212: 1798-1805. PMID: 25995193, PMCID: PMC4633762, DOI: 10.1093/infdis/jiv299.Peer-Reviewed Original ResearchMeSH KeywordsAdultBacterial ProteinsCohort StudiesHaemophilus InfectionsHaemophilus influenzaeHumansPulmonary Disease, Chronic ObstructiveRespiratory Tract InfectionsSerine EndopeptidasesSputumConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseH. influenzaeIgA protease genePulmonary diseaseHuman airwaysHaemophilus influenzaeIgA proteaseH. influenzae infectionsHuman respiratory epithelial cellsHuman IgA1Respiratory epithelial cellsInfluenzae infectionRespiratory tractIgA protease activitySputum samplesClinical settingInfluenzaeEpithelial cellsInfectionAirwayIgA1 fragmentsDiseaseIgA1Protease gene