2024
Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs
Kunisch F, Campobasso C, Wagemans J, Yildirim S, Chan B, Schaudinn C, Lavigne R, Turner P, Raschke M, Trampuz A, Gonzalez Moreno M. Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs. Nature Communications 2024, 15: 8572. PMID: 39362854, PMCID: PMC11450229, DOI: 10.1038/s41467-024-52595-w.Peer-Reviewed Original ResearchConceptsResistance trade-offBacteriophage host rangeViruses of bacteriaHuman microbial infectionsMultidrug-resistant bacterial infectionsTwo-phage cocktailMultidrug-resistant Pseudomonas aeruginosa strainsLytic bacteriophagesBiofilm-associatedEvolution assaysPlanktonic culturesBacteriophage cocktailHost rangeBacteriophageHost spectrumBacteriophage therapyCocktail designCombat biofilmsTreated bacteriaMicrobial infectionsAntimicrobial efficacyBacterial suppressionPolymerase chain reactionBacterial infectionsClinical outcomesLytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells
Zamora P, Reidy T, Armbruster C, Sun M, Van Tyne D, Turner P, Koff J, Bomberger J. Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells. PLOS Biology 2024, 22: e3002566. PMID: 38652717, PMCID: PMC11037538, DOI: 10.1371/journal.pbio.3002566.Peer-Reviewed Original ResearchConceptsLytic phagesLytic bacteriophagesPhage therapyAirway epithelial cellsPseudomonas aeruginosa phagesEpithelial cellsMultidrug resistanceAirway epitheliumCystic fibrosisProinflammatory cytokinesHuman respiratory epithelial cellsPhage exposurePhage familiesMammalian cell responsesHuman airway epithelial cellsInternalized phageTreat multidrug-resistantPhageBacterial isolatesTranscriptional profilesRespiratory epithelial cellsHuman hostChronic respiratory disordersBacterial biofilmsBacteriophageOptimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University
Würstle S, Lee A, Kortright K, Winzig F, An W, Stanley G, Rajagopalan G, Harris Z, Sun Y, Hu B, Blazanin M, Hajfathalian M, Bollyky P, Turner P, Koff J, Chan B. Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University. Scientific Reports 2024, 14: 2657. PMID: 38302552, PMCID: PMC10834462, DOI: 10.1038/s41598-024-52192-3.Peer-Reviewed Original ResearchMeSH KeywordsBacteriophagesHumansPhage TherapyPseudomonas aeruginosaPseudomonas InfectionsPseudomonas PhagesUniversitiesConceptsEvolutionary selection pressurePhage characterizationPhage therapyPersistent bacterial infectionsBacteriophage therapyPhageSelection pressurePseudomonas aeruginosaInvestigational new drug applicationBacterial infectionsNew Drug ApplicationTherapyDrug applicationClinical applicationAutographiviridaeBacteriaPotential strategy
2023
Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance
Oromí-Bosch A, Antani J, Turner P. Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance. Annual Review Of Virology 2023, 10: 503-524. PMID: 37268007, DOI: 10.1146/annurev-virology-012423-110530.Peer-Reviewed Original ResearchConceptsPhage therapyPhage resistanceBacterial resistanceEvolution of phage resistancePhage-resistant bacteriaEvolution of bacterial resistanceBacteria-specific virusesTreatment of intractable infectionsAlternative antimicrobial strategiesPersonalized medicine treatmentsPhage strategyClinically favorable outcomesBacterial pathogensBacterial populationsPhageTarget bacteriaAntibiotic resistanceAntimicrobial strategiesIntractable infectionsWaning efficacyFavorable outcomeBacterial infectionsBacteriaTherapyPatient treatmentExperimental Evolution of the TolC-Receptor Phage U136B Functionally Identifies a Tail Fiber Protein Involved in Adsorption through Strong Parallel Adaptation
Burmeister A, Tzintzun-Tapia E, Roush C, Mangal I, Barahman R, Bjornson R, Turner P. Experimental Evolution of the TolC-Receptor Phage U136B Functionally Identifies a Tail Fiber Protein Involved in Adsorption through Strong Parallel Adaptation. Applied And Environmental Microbiology 2023, 89: e00079-23. PMID: 37191555, PMCID: PMC10304864, DOI: 10.1128/aem.00079-23.Peer-Reviewed Original ResearchConceptsExperimental evolutionPhage populationsParallel molecular evolutionWhole-population sequencingAntibiotic resistance proteinsTail fiber proteinE. coli hostPhage evolutionEvolutionary potentialMolecular evolutionPhage genotypesTolC proteinParallel adaptationProtein geneAntibiotic resistanceExperimental populationsBacterial diversitySelection pressureBacterial hostsColi hostFiber proteinBacterial populationsBacterial cellsPhage resistancePhage dynamics
2022
Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.
Winzig F, Gandhi S, Lee A, Würstle S, Stanley G, Capuano I, Neuringer I, Koff J, Turner P, Chan B. Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter. The Yale Journal Of Biology And Medicine 2022, 95: 413-427. PMID: 36568830, PMCID: PMC9765334.Peer-Reviewed Original ResearchConceptsCF patientsCystic fibrosisChronic pulmonary infectionGlobal public health threatBacterial lung infectionsChallenging clinical problemPublic health threatChronic bacterial lung infectionsPulmonary infectionRespiratory statusLung infectionClinical problemBacteriophage therapyInfectionAntimicrobial-resistant bacteriaTherapyHealth threatPhage therapyPatientsAMR infectionsResistant bacteriaLytic bacteriophagesPossible benefitsChemical antibioticsCurrent study
2021
Community context matters for bacteria-phage ecology and evolution
Blazanin M, Turner P. Community context matters for bacteria-phage ecology and evolution. The ISME Journal: Multidisciplinary Journal Of Microbial Ecology 2021, 15: 3119-3128. PMID: 34127803, PMCID: PMC8528888, DOI: 10.1038/s41396-021-01012-x.Peer-Reviewed Original ResearchConceptsBacteria-phage systemsEvolutionary effectsBacteria-phage coevolutionValuable biological modelUnderstanding of bacteriaAdditional bacterial speciesMechanisms of adaptationEcological interactionsPleiotropic consequencesComplex communitiesCoevolutionary dynamicsBacterial speciesEcologyPhagesBacteriaBiological modelsSymbiosesCoevolutionCommunity contextSpeciesEvolutionMultispeciesCommunityAdaptationCommunity presenceEffects of historical co‐infection on host shift abilities of exploitative and competitive viruses
Singhal S, Turner P. Effects of historical co‐infection on host shift abilities of exploitative and competitive viruses. Evolution 2021, 75: 1878-1888. PMID: 33969482, DOI: 10.1111/evo.14263.Peer-Reviewed Original ResearchConceptsNovel hostRNA viral pathogensHost population densityViral growthPhage genotypesCo-infecting virusesHost specificityIntracellular competitionHost exploitationHost genotypeEcological historyOriginal hostInfected bacteriaRNA bacteriophagesRapid evolutionEmergence potentialHostGrowth curvesPopulation densityEquivalent growthViral pathogensClonesInfectivity differencesGenotypesCompetitive viruses
2012
Selective Pressure Causes an RNA Virus to Trade Reproductive Fitness for Increased Structural and Thermal Stability of a Viral Enzyme
Dessau M, Goldhill D, McBride R, Turner PE, Modis Y. Selective Pressure Causes an RNA Virus to Trade Reproductive Fitness for Increased Structural and Thermal Stability of a Viral Enzyme. PLOS Genetics 2012, 8: e1003102. PMID: 23209446, PMCID: PMC3510033, DOI: 10.1371/journal.pgen.1003102.Peer-Reviewed Original ResearchConceptsFitness tradeoffsPleiotropic mutationMolecular basisRNA virusesSingle amino acid substitutionAmino acid substitutionsIndividual point mutationsEvolutionary tugPleiotropic phenotypesExperimental evolutionAntagonistic pleiotropyEvolutionary biologyProtein functionLytic transglycosylaseNatural selectionProtein P5Reproductive fitnessStructural biologySelective pressureMutational substitutionsHeat shockProtein structureCapsid assemblyAcid substitutionsBacteriophage Φ6
2005
Widespread genetic exchange among terrestrial bacteriophages
Silander OK, Weinreich DM, Wright KM, O'Keefe KJ, Rang CU, Turner PE, Chao L. Widespread genetic exchange among terrestrial bacteriophages. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 19009-19014. PMID: 16365305, PMCID: PMC1323146, DOI: 10.1073/pnas.0503074102.Peer-Reviewed Original ResearchConceptsGenetic exchangeLinkage disequilibriumBiological species conceptWidespread genetic exchangeGenomic mutation rateFrequent genetic reassortmentSingle host cellGroup of phagesBiogeography studiesSexual populationsGenetic structureSpecies conceptWild populationsNucleotide divergenceFrequent reassortmentDsRNA genomeBacteriophage populationsDegenerate sitesRecombination eventsNumerical dominanceMutation rateHost cellsGenetic reassortmentUnrelated individualsBacteriophages