Featured Publications
Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
Chaguza C, Senghore M, Bojang E, Gladstone RA, Lo SW, Tientcheu PE, Bancroft RE, Worwui A, Foster-Nyarko E, Ceesay F, Okoi C, McGee L, Klugman KP, Breiman RF, Barer MR, Adegbola RA, Antonio M, Bentley SD, Kwambana-Adams BA. Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation. Nature Communications 2020, 11: 3442. PMID: 32651390, PMCID: PMC7351774, DOI: 10.1038/s41467-020-17327-w.Peer-Reviewed Original ResearchMeSH KeywordsEvolution, MolecularGeneticsGenome, BacterialHumansPneumococcal InfectionsStreptococcus pneumoniaeWhole Genome SequencingConceptsNatural colonisationHost microevolutionNucleotide substitution ratesWhole-genome sequencingGenomic evolutionNeutral evolutionGenetic diversityHomologous recombinationParallel evolutionGenomic changesAdhesion genesSubstitution ratesHuman-adapted pathogenMicroevolutionStrain variantsColonisationImmune evasionStreptococcus pneumoniaeAntibiotic resistanceGenesEvolutionSequencingDiversityNasopharyngeal carriageBacteria
2024
Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi.
Cave R, Kalizang'oma A, Chaguza C, Mwalukomo T, Kamng’ona A, Brown C, Msefula J, Bonomali F, Nyirenda R, Swarthout T, Kwambana-Adams B, French N, Heyderman R. Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi. Microbial Genomics 2024, 10 PMID: 38896467, DOI: 10.1099/mgen.0.001264.Peer-Reviewed Original ResearchConceptsGenes associated with antibiotic resistanceAntibiotic resistancePneumococcal conjugate vaccineVirulence factor expressionDNA binding sitesVaccine serotypesB-type domainWzy proteinsPolysaccharide locusConjugate vaccineCarriage of vaccine serotypesIntroduction of pneumococcal conjugate vaccinesCapsule polysaccharideEmergent lineagesGenetic changesStreptococcus pneumoniae</i>Vaccination coverageLineagesPersistent carriageGenotypic changesBinding sitesSerotypesMultidrug resistanceT mutationVirulence
2022
Pneumococcal within-host diversity during colonization, transmission and treatment
Tonkin-Hill G, Ling C, Chaguza C, Salter SJ, Hinfonthong P, Nikolaou E, Tate N, Pastusiak A, Turner C, Chewapreecha C, Frost SDW, Corander J, Croucher NJ, Turner P, Bentley SD. Pneumococcal within-host diversity during colonization, transmission and treatment. Nature Microbiology 2022, 7: 1791-1804. PMID: 36216891, PMCID: PMC9613479, DOI: 10.1038/s41564-022-01238-1.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsCarrier StateChildHumansNasopharynxPneumococcal InfectionsSerogroupStreptococcus pneumoniaeConceptsAntimicrobial treatmentAbsence of treatmentMultidrug-resistant bacteriumNasopharyngeal samplesElevated riskGold standard methodTreatment dataStreptococcus pneumoniaePersistent colonizationPneumococcal populationGenomic surveillanceInter-strain competitionTreatmentDeep sequencingInfantsResistant lineagesElevated ratesBacterial pathogensFirst yearMothersSensitive bacteriaTransmission chainSurveillanceSusceptible lineagesPathogensComparative Genomics of Disease and Carriage Serotype 1 Pneumococci
Chaguza C, Ebruke C, Senghore M, Lo S, Tientcheu P, Gladstone R, Tonkin-Hill G, Cornick J, Yang M, Worwui A, McGee L, Breiman R, Klugman K, Kadioglu A, Everett D, Mackenzie G, Croucher N, Roca A, Kwambana-Adams B, Antonio M, Bentley S. Comparative Genomics of Disease and Carriage Serotype 1 Pneumococci. Genome Biology And Evolution 2022, 14: evac052. PMID: 35439297, PMCID: PMC9048925, DOI: 10.1093/gbe/evac052.Peer-Reviewed Original ResearchMeSH KeywordsCarrier StateGenome-Wide Association StudyGenomicsHumansNasopharynxPneumococcal InfectionsPneumococcal VaccinesSerogroupStreptococcus pneumoniaeConceptsGenomic variationGenome-wide association studiesComparative genomicsGenetic variationLineage distributionAssociation studiesPhenotypic variabilityPathogen surveillanceSystemic tissuesIsolatesSerotype 1GenomicsLineagesGeneticsMinimal effectVariationInvasivenessSerotype 1 pneumococciIsolationInvasive diseaseA Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV
Ndlangisa K, du Plessis M, Lo S, de Gouveia L, Chaguza C, Antonio M, Kwambana-Adams B, Cornick J, Everett D, Dagan R, Hawkins P, Beall B, Corso A, Grassi Almeida S, Ochoa T, Obaro S, Shakoor S, Donkor E, Gladstone R, Ho P, Paragi M, Doiphode S, Srifuengfung S, Ford R, Moïsi J, Saha S, Bigogo G, Sigauque B, Eser Ö, Elmdaghri N, Titov L, Turner P, Kumar K, Kandasamy R, Egorova E, Ip M, Breiman R, Klugman K, McGee L, Bentley S, von Gottberg A, The Global Pneumococcal Sequencing Consortium. A Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV. Microbial Genomics 2022, 8: 000746. PMID: 35384831, PMCID: PMC9453074, DOI: 10.1099/mgen.0.000746.Peer-Reviewed Original ResearchHumansPneumococcal InfectionsPneumococcal VaccinesSerogroupSouth AfricaStreptococcus pneumoniaeVaccines, ConjugateA new perspective on ancient Mitis group streptococcal genetics
Belman S, Chaguza C, Kumar N, Lo S, Bentley SD. A new perspective on ancient Mitis group streptococcal genetics. Microbial Genomics 2022, 8: 000753. PMID: 35225216, PMCID: PMC8942026, DOI: 10.1099/mgen.0.000753.Peer-Reviewed Original ResearchMeSH KeywordsHumansPneumococcal VaccinesStreptococcusStreptococcus mitisStreptococcus pneumoniaeVirulence FactorsConceptsCommensal speciesVirulence factorsPathogenic speciesSpecific virulence factorsMitis groupHost-microbe interactionsMajor virulence factorInvasive diseaseLeading causeOral cavityVaccine antigensEvolutionary divergenceExtant speciesEvolutionary historyExtant strainsStreptococcus pneumoniaeSuch genesAncient genomesSynthesis genesGene databaseIndividual speciesPolysaccharide capsuleZinc metalloproteasesStable maintenanceObligate bacteriaWidespread sharing of pneumococcal strains in a rural African setting: proximate villages are more likely to share similar strains that are carried at multiple timepoints
Senghore M, Chaguza C, Bojang E, Tientcheu P, Bancroft R, Lo S, Gladstone R, McGee L, Worwui A, Foster-Nyarko E, Ceesay F, Okoi C, Klugman K, Breiman R, Bentley S, Adegbola R, Antonio M, Hanage W, Kwambana-Adams B. Widespread sharing of pneumococcal strains in a rural African setting: proximate villages are more likely to share similar strains that are carried at multiple timepoints. Microbial Genomics 2022, 8: 000732. PMID: 35119356, PMCID: PMC8942022, DOI: 10.1099/mgen.0.000732.Peer-Reviewed Original ResearchMeSH KeywordsAfricaHumansInfantMicrobiotaNasopharynxPneumococcal InfectionsRural PopulationSerogroupStreptococcus pneumoniaeWhole Genome SequencingConceptsTransmission dynamicsRural African settingLogistic regression modelsPCV7 serotypesLongitudinal cohortCarriage episodesUnique serotypesPneumococcal strainsInfantsPairwise SNP distanceMultiple timepointsAfrican settingSNP distanceSustained colonizationRegression modelsSaharan AfricaCarriageSerotypesRural AfricaIntra-strain diversityPneumococcal genomeNeighbouring villagesCohort
2021
Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms
Chaguza C, Yang M, Jacques L, Bentley S, Kadioglu A. Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms. Trends In Microbiology 2021, 30: 581-592. PMID: 34949516, PMCID: PMC7613904, DOI: 10.1016/j.tim.2021.11.007.Peer-Reviewed Original ResearchStreptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis
Kalizang'oma A, Chaguza C, Gori A, Davison C, Beleza S, Antonio M, Beall B, Goldblatt D, Kwambana-Adams B, Bentley SD, Heyderman RS. Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis. Microbial Genomics 2021, 7: 000622. PMID: 34550067, PMCID: PMC8715442, DOI: 10.1099/mgen.0.000622.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBeta-Lactam ResistanceDrug Resistance, BacterialGene Transfer, HorizontalGenes, BacterialHumansMicrobial Sensitivity TestsNasopharynxPenicillin-Binding ProteinsPenicillinsPhylogenyPneumococcal InfectionsPneumococcal VaccinesSerogroupStreptococcusStreptococcus mitisStreptococcus oralisStreptococcus pneumoniaeWhole Genome SequencingConceptsMinimum inhibitory concentrationPneumococcal vaccine programsFirst-line treatmentHigh minimum inhibitory concentrationsStreptococcus pneumoniae serotypesPneumococcal population structurePneumococcal serotypes 6ABeta-lactam antibioticsLonger carriage durationBeta-lactam resistanceImportant global pathogenPneumococcal diseaseBacterial pneumoniaPneumococcal serotypesVaccine programSerotypes 6APneumoniae serotypesΒ-lactam susceptibilityPenicillin-binding protein (PBP) genesHuman nasopharynxCarriage durationCommensal streptococciCommon recipientInhibitory concentrationStreptococciPneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models
Green AE, Howarth D, Chaguza C, Echlin H, Langendonk RF, Munro C, Barton TE, Hinton J, Bentley SD, Rosch JW, Neill DR. Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models. Molecular Biology And Evolution 2021, 38: 2209-2226. PMID: 33502519, PMCID: PMC8136498, DOI: 10.1093/molbev/msab018.Peer-Reviewed Original ResearchConceptsNasopharyngeal carriageWhole genomic comparative analysis of Streptococcus pneumoniae serotype 1 isolates causing invasive and non-invasive infections among children under 5 years in Casablanca, Morocco
Nzoyikorera N, Diawara I, Fresia P, Maaloum F, Katfy K, Nayme K, Maaloum M, Cornick J, Chaguza C, Timinouni M, Belabess H, Zerouali K, Elmdaghri N. Whole genomic comparative analysis of Streptococcus pneumoniae serotype 1 isolates causing invasive and non-invasive infections among children under 5 years in Casablanca, Morocco. BMC Genomics 2021, 22: 39. PMID: 33413118, PMCID: PMC7792055, DOI: 10.1186/s12864-020-07316-0.Peer-Reviewed Original Research
2020
Lower Density and Shorter Duration of Nasopharyngeal Carriage by Pneumococcal Serotype 1 (ST217) May Explain Its Increased Invasiveness over Other Serotypes
Bricio-Moreno L, Chaguza C, Yahya R, Shears RK, Cornick JE, Hokamp K, Yang M, Neill DR, French N, Hinton JCD, Everett DB, Kadioglu A. Lower Density and Shorter Duration of Nasopharyngeal Carriage by Pneumococcal Serotype 1 (ST217) May Explain Its Increased Invasiveness over Other Serotypes. MBio 2020, 11: e00814-20. PMID: 33293378, PMCID: PMC7733939, DOI: 10.1128/mbio.00814-20.Peer-Reviewed Original ResearchConceptsInvasive pneumococcal diseaseNasopharyngeal carriageSerotype 1Invasive diseaseDisease progressionPneumococcal strainsInvasive pneumococcal disease casesQueen Elizabeth Central HospitalMajor causePneumococcal disease casesPneumococcal serotype 1Health care systemPneumococcal diseaseCentral HospitalVaccine efficacyInvasive infectionsInvasive pneumoniaCommon causeMurine modelMouse modelDisease casesCarrier stateHuman nasopharynxPneumoniaRNA sequencing analysisHypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity
Panagiotou S, Chaguza C, Yahya R, Audshasai T, Baltazar M, Ressel L, Khandaker S, Alsahag M, Mitchell TJ, Prudhomme M, Kadioglu A, Yang M. Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity. Scientific Reports 2020, 10: 17313. PMID: 33057054, PMCID: PMC7560715, DOI: 10.1038/s41598-020-73454-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsFemaleHemolysisHumansMiceSerogroupStreptococcus pneumoniaeStreptolysinsVirulenceConceptsPneumococcal serotype 1Invasive pneumococcal diseaseSerotype 1Haemolytic activityVivo mouse modelDetectable haemolytic activityNeutrophil-mediated phagocytosisPneumococcal diseaseCommon causeInfection doseHuman reservoirMouse modelRapid onsetStreptococcus pneumoniaeDisease symptomsLethal doseClonal typesVirulence propertiesGlobal pathogenST306IgA proteaseSymptomsSequence typesMiceDoseBacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism
Chaguza C, Yang M, Cornick JE, du Plessis M, Gladstone RA, Kwambana-Adams BA, Lo SW, Ebruke C, Tonkin-Hill G, Peno C, Senghore M, Obaro SK, Ousmane S, Pluschke G, Collard JM, Sigaùque B, French N, Klugman KP, Heyderman RS, McGee L, Antonio M, Breiman RF, von Gottberg A, Everett DB, Kadioglu A, Bentley SD. Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. Communications Biology 2020, 3: 559. PMID: 33033372, PMCID: PMC7545184, DOI: 10.1038/s42003-020-01290-9.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPneumococcal serotype 1Genetic variationBacterial genome-wide association studiesAssociation studiesSerotype 1Central nervous system infectionSignificant genotype-phenotype associationsNervous system infectionGenotype-phenotype associationsHelicase proteinPopulation structureCNS infectionsSystem infectionNegligible heritabilityMeningitis outbreakCNS tissueCerebrospinal fluidImmune evasionSerotype 1 strainPneumococcal survivalPolygenic etiologySmall effect sizesMeningitisTropism
2019
Early Signals of Vaccine-driven Perturbation Seen in Pneumococcal Carriage Population Genomic Data
Chaguza C, Heinsbroek E, Gladstone RA, Tafatatha T, Alaerts M, Peno C, Cornick JE, Musicha P, Bar-Zeev N, Kamng’ona A, Kadioglu A, McGee L, Hanage WP, Breiman RF, Heyderman RS, French N, Everett DB, Bentley SD. Early Signals of Vaccine-driven Perturbation Seen in Pneumococcal Carriage Population Genomic Data. Clinical Infectious Diseases 2019, 70: 1294-1303. PMID: 31094423, PMCID: PMC7768739, DOI: 10.1093/cid/ciz404.Peer-Reviewed Original ResearchMeSH KeywordsCarrier StateChildHumansInfantMalawiMetagenomicsNasopharynxPneumococcal InfectionsPneumococcal VaccinesSerogroupStreptococcus pneumoniaeVaccines, ConjugateConceptsYears of ageVaccine serotypesWhole-genome sequencingHigh disease burdenAntibiotic resistanceLow-income settingsPCV introductionReplacement serotypesVT serotypesPneumococcal diseaseNonvaccine serotypesCarriage rateDisease burdenPneumococcal isolatesSerotype dynamicsContinued surveillancePCV effectsAge groupsSerotypesSerotype diversityAgeVaccineResistant lineagesPCVChildren
2017
Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia
Bricio-Moreno L, Ebruke C, Chaguza C, Cornick J, Kwambana-Adams B, Yang M, Mackenzie G, Wren BW, Everett D, Antonio M, Kadioglu A. Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia. The Journal Of Infectious Diseases 2017, 216: 1318-1327. PMID: 28968897, PMCID: PMC5853340, DOI: 10.1093/infdis/jix472.Peer-Reviewed Original ResearchAnimalsCarrier StateDisease Models, AnimalGambiaGenetic VariationGenome, BacterialGenomicsHemolysisHost-Pathogen InteractionsHumansMaleMiceMultilocus Sequence TypingNasopharynxPhenotypePneumococcal InfectionsPneumonia, PneumococcalPolymorphism, Single NucleotideSerotypingStreptococcus pneumoniaeVirulencePopulation genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi
Chaguza C, Cornick JE, Andam CP, Gladstone RA, Alaerts M, Musicha P, Peno C, Bar-Zeev N, Kamng'ona AW, Kiran AM, Msefula CL, McGee L, Breiman RF, Kadioglu A, French N, Heyderman RS, Hanage WP, Bentley SD, Everett DB. Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi. Vaccine 2017, 35: 4594-4602. PMID: 28711389, PMCID: PMC5571440, DOI: 10.1016/j.vaccine.2017.07.009.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultBacterial CapsulesChildChild, PreschoolDrug Resistance, Multiple, BacterialEvolution, MolecularFemaleGenome, BacterialHigh-Throughput Nucleotide SequencingHumansInfantInfant, NewbornMalawiMalePneumococcal InfectionsPneumococcal VaccinesPrevalenceRetrospective StudiesSerogroupSerotypingStreptococcus pneumoniaeVaccinationVaccines, ConjugateYoung AdultConceptsPneumococcal conjugate vaccineMDR ratePneumococcal isolatesHigher MDR rateImplementation of PCV13Prevalence of serotypesNon-vaccine serotypesInvasive pneumococcal isolatesGood infection preventionAntibiotic resistance ratesAntibiotic resistanceAbsence of vaccinesReplacement serotypesSerotype replacementInvasive pneumococciPneumococcal infectionConjugate vaccineSerotype 12FDisease burdenInfection preventionSerotype prevalenceHigh prevalenceInvasive isolatesContinued surveillanceResistance ratesGenomic Epidemiology of Penicillin-Nonsusceptible Pneumococci with Nonvaccine Serotypes Causing Invasive Disease in the United States
Andam CP, Mitchell PK, Callendrello A, Chang Q, Corander J, Chaguza C, McGee L, Beall BW, Hanage WP. Genomic Epidemiology of Penicillin-Nonsusceptible Pneumococci with Nonvaccine Serotypes Causing Invasive Disease in the United States. Journal Of Clinical Microbiology 2017, 55: 1104-1115. PMID: 28100596, PMCID: PMC5377837, DOI: 10.1128/jcm.02453-16.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolEpidemiological MonitoringEvolution, MolecularFemaleGenome, BacterialGenotypeHumansInfantInfant, NewbornMaleMiddle AgedMolecular EpidemiologyPenicillin ResistancePneumococcal InfectionsSequence Analysis, DNASerogroupStreptococcus pneumoniaeUnited StatesYoung AdultConceptsActive Bacterial Core surveillancePneumococcal Molecular Epidemiology NetworkNonvaccine typesVaccine typesPenicillin-nonsusceptible pneumococciAntibiotic-resistant strainsNVT pneumococciNonvaccine serotypesSerotype 35BPneumococcal serotypesInvasive diseaseSerogroups 23Core surveillanceEpidemiology NetworkDisease controlDisease prevalencePNSPGenomic epidemiologyFuture surveillanceVaccinationSerotypesResistant clonesSerotype switchingPneumococciDiseaseThe global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1
Cornick JE, Bishop Ö, Yalcin F, Kiran AM, Kumwenda B, Chaguza C, Govindpershad S, Ousmane S, Senghore M, du Plessis M, Pluschke G, Ebruke C, McGee L, Sigaùque B, Collard JM, Bentley SD, Kadioglu A, Antonio M, von Gottberg A, French N, Klugman KP, Heyderman RS, Alderson M, Everett DB, consortium F. The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1. Vaccine 2017, 35: 972-980. PMID: 28081968, PMCID: PMC5287219, DOI: 10.1016/j.vaccine.2016.12.037.Peer-Reviewed Original ResearchConceptsProtein vaccine candidatePneumococcal protein vaccinesProtein vaccineVaccine candidatesSerotype 1Multi-valent vaccinesSerotype 1 pneumococciPneumococcal conjugate vaccineHuman immune responseImportant pneumococcal serotypesConjugate vaccinePneumococcal diseasePneumococcal serotypesVaccine interventionsCommon causeImmune responseStudy populationAllelic variantsTarget antigenVaccineS. pneumoniae TIGR4Pneumococcal populationIntervention strategiesPCPADifferent allelic variants
2016
Understanding pneumococcal serotype 1 biology through population genomic analysis
Chaguza C, Cornick JE, Harris SR, Andam CP, Bricio-Moreno L, Yang M, Yalcin F, Ousmane S, Govindpersad S, Senghore M, Ebruke C, Du Plessis M, Kiran AM, Pluschke G, Sigauque B, McGee L, Klugman KP, Turner P, Corander J, Parkhill J, Collard JM, Antonio M, von Gottberg A, Heyderman RS, French N, Kadioglu A, Hanage WP, Everett DB, Bentley SD, for the PAGe Consortium. Understanding pneumococcal serotype 1 biology through population genomic analysis. BMC Infectious Diseases 2016, 16: 649. PMID: 27821148, PMCID: PMC5100261, DOI: 10.1186/s12879-016-1987-z.Peer-Reviewed Original ResearchConceptsDisease burdenPneumococcal disease burdenSerotype 1 pneumococciSub-Saharan AfricaHigh prevalenceHuman nasopharynxAfrican isolatesLow-income countriesSerotype 1Longer durationFurther studiesTetracycline resistanceBiological mechanismsST217West African isolatesDifferent geographical regionsSuccessful clones