Featured Publications
Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion
Chaguza C, Jamrozy D, Bijlsma M, Kuijpers T, van de Beek D, van der Ende A, Bentley S. Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion. Nature Communications 2022, 13: 4215. PMID: 35864107, PMCID: PMC9304382, DOI: 10.1038/s41467-022-31858-4.Peer-Reviewed Original ResearchConceptsPopulation genomicsMicrobial population genomicsGroup B streptococciWide association studyPopulation structureGenetic variationGenetic signaturesCapsule biosynthesis locusDisease onset timeAssociation studiesB streptococciInvasive neonatal GBS diseaseNeonatal GBS diseaseGenomicsPathogen surveillanceAcute invasive diseaseGeneticsOnset timeDisease pathogenesisGBS diseasePreterm birthTissue infectionsDisease burdenDisease onsetInvasive diseaseRecombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule
Chaguza C, Andam CP, Harris SR, Cornick JE, Yang M, Bricio-Moreno L, Kamng’ona A, Parkhill J, French N, Heyderman RS, Kadioglu A, Everett DB, Bentley SD, Hanage WP. Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule. MBio 2016, 7: e01053-16. PMID: 27677790, PMCID: PMC5040112, DOI: 10.1128/mbio.01053-16.Peer-Reviewed Original ResearchPneumococcal conjugate vaccineInvasive pneumococcal diseasePrevalence of carriageCarriage durationCarriage prevalenceComplex polysaccharide capsulePolysaccharide capsuleVaccine escape variantsSerotype-specific responsesDifferent pneumococcal serotypesResource-poor settingsLonger carriage durationPneumococcal diseaseConjugate vaccinePneumococcal serotypesEscape variantsUnivariate analysisHigh burdenMultivariate analysisStreptococcus pneumoniaeDrug resistanceClinical interventionsPneumococciPrevalenceVaccineWithin-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 ResearchConceptsNatural colonisationHost microevolutionNucleotide substitution ratesWhole-genome sequencingGenomic evolutionNeutral evolutionGenetic diversityHomologous recombinationParallel evolutionGenomic changesAdhesion genesSubstitution ratesHuman-adapted pathogenMicroevolutionStrain variantsColonisationImmune evasionStreptococcus pneumoniaeAntibiotic resistanceGenesEvolutionSequencingDiversityNasopharyngeal carriageBacteria
2024
Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections
Li K, Chaguza C, Stamp J, Chew Y, Chen N, Ferguson D, Pandya S, Kerantzas N, Schulz W, Initiative Y, Hahn A, Ogbunugafor C, Pitzer V, Crawford L, Weinberger D, Grubaugh N. Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections. PLOS Computational Biology 2024, 20: e1012469. PMID: 39288189, PMCID: PMC11432881, DOI: 10.1371/journal.pcbi.1012469.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle-nucleotide polymorphismsAssociation studiesWhole-genome sequencingAmino acid changesSingle nucleotide polymorphismsPairs of substitutionsViral copiesEpistasis testsGenome sequenceGenetic variationSpike geneAcid changesViral genomeNucleotide polymorphismsSARS-CoV-2Detect interactionsHost factorsVirus copiesCopyInfection dynamicsRT-qPCRPolymorphismOmicron BASARS-CoV-2 infectionPopulation genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases
Kalizang’oma A, Richard D, Kwambana-Adams B, Coelho J, Broughton K, Pichon B, Hopkins K, Chalker V, Beleza S, Bentley S, Chaguza C, Heyderman R. Population genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases. Nature Communications 2024, 15: 7812. PMID: 39242612, PMCID: PMC11379897, DOI: 10.1038/s41467-024-52120-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnti-Bacterial AgentsBacteremiaDrug Resistance, BacterialEndocarditisEndocarditis, BacterialFemaleGenetic VariationGenome, BacterialGenomicsHumansIrelandMaleMiddle AgedPhylogenyStreptococcal InfectionsStreptococcus mitisUnited KingdomVirulenceVirulence FactorsWhole Genome SequencingConceptsGenetic diversityBloodstream infectionsInvestigate genetic diversityInfective endocarditisStreptococcus mitisPneumococcal virulence genesS. mitisPopulation genomicsInfective endocarditis casesGenome sequenceVirulence genesGenomic epidemiologyCarriage strainsResistant lineagesPathogenic natureIE casesAntimicrobial resistanceEndocarditis casesIE incidenceLineagesGenomeIsolatesPathogensClinicPatientsPan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study
Thorpe H, Pesonen M, Corbella M, Pesonen H, Gaiarsa S, Boinett C, Tonkin-Hill G, Mäklin T, Pöntinen A, MacAlasdair N, Gladstone R, Arredondo-Alonso S, Kallonen T, Jamrozy D, Lo S, Chaguza C, Blackwell G, Honkela A, Schürch A, Willems R, Merla C, Petazzoni G, Feil E, Cambieri P, Thomson N, Bentley S, Sassera D, Corander J. Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study. The Lancet Microbe 2024, 100890. PMID: 39178869, DOI: 10.1016/s2666-5247(24)00113-7.Peer-Reviewed Original ResearchIntensive care unitProspective cohort studyCohort studyHospital transmissionWhole-genome sequencingCare unitDeep sequencing approachSingle nucleotide polymorphism distancesNosocomial bacterial pathogensInfection control measuresAntimicrobial resistance genesPathogenic speciesBacterial pathogensDeep sequencingEffectiveness of infection control measuresAntimicrobial resistance genes prevalenceAcinetobacter baumanniiNosocomial infectionsStreptococcus pneumoniaeSan Matteo HospitalClinical surveillanceWithin-patientKlebsiella pneumoniaeCo-colonisationGene prevalenceGenomic insights into the 2022–2023Vibrio cholerae outbreak in Malawi
Chaguza C, Chibwe I, Chaima D, Musicha P, Ndeketa L, Kasambara W, Mhango C, Mseka U, Bitilinyu-Bangoh J, Mvula B, Kipandula W, Bonongwe P, Munthali R, Ngwira S, Mwendera C, Kalizang’oma A, Jambo K, Kambalame D, Kamng’ona A, Steele A, Chauma-Mwale A, Hungerford D, Kagoli M, Nyaga M, Dube Q, French N, Msefula C, Cunliffe N, Jere K. Genomic insights into the 2022–2023Vibrio cholerae outbreak in Malawi. Nature Communications 2024, 15: 6291. PMID: 39060226, PMCID: PMC11282309, DOI: 10.1038/s41467-024-50484-w.Peer-Reviewed Original ResearchConceptsSerogroup O1 strainsIntegrative conjugative elementsPhylogenetic reconstructionPopulation genomicsGenomic insightsOutbreak isolatesVirulence elementsConjugative elementsO1 strainsVibrio choleraeOutbreak strainEl TorAntimicrobial resistanceCholera outbreaksO1 OgawaIsolatesCholeraStrainCtxB7 genotypesProphageGenomeVirulenceCtxB7SublineagesLineagesMolecular Epidemiology of Isoniazid-resistant M tuberculosis in Port-au-Prince, Haiti
Walsh K, Lee M, Chaguza C, Pamphile W, Royal G, Escuyer V, Pape J, Fitzgerald D, Cohen T, Ocheretina O. Molecular Epidemiology of Isoniazid-resistant M tuberculosis in Port-au-Prince, Haiti. Open Forum Infectious Diseases 2024, 11: ofae421. PMID: 39119477, PMCID: PMC11306977, DOI: 10.1093/ofid/ofae421.Peer-Reviewed Original ResearchCulture-positive pulmonary tuberculosisIsoniazid-resistant isolatesHR-TBIsoniazid-resistant M. tuberculosisPulmonary tuberculosisIsoniazid resistanceMutations associated with INH resistanceTransmission clustersGenoType MTBDRplus assayINH-resistant isolatesIsoniazid-susceptible isolatesPhenotypic isoniazid resistanceRifampin-susceptible tuberculosisSingle nucleotide polymorphism distancesMolecular epidemiologyAssociated with poor treatment outcomesWhole-genome sequencingM. tuberculosisPutative transmission clustersPoor treatment outcomesMTBDRplus assayGenoType MTBDRplusCulture-based testsINH resistanceTuberculosis clinicGenetic markers associated with host status and clonal expansion of Group B Streptococcus in the Netherlands
Khan U, Dyster V, Chaguza C, van Sorge N, van de Beek D, Man K, Bentley S, Bijlsma M, Jamrozy D. Genetic markers associated with host status and clonal expansion of Group B Streptococcus in the Netherlands. Frontiers In Microbiology 2024, 15: 1410651. DOI: 10.3389/fmicb.2024.1410651.Peer-Reviewed Original ResearchGroup B streptococciDisease isolatesCarriage isolatesCC17 isolatesClonal complexesDistribution of genetic markersPrevalence of antimicrobial resistance genesWhole-genome sequencingMobile genetic elementsAntimicrobial resistance genesAssociated with invasive diseaseGBS populationB streptococciInvasive diseaseClonal expansion eventsGenome sequenceExpansion eventsGenetic elementsGenomic analysisGenetic markersResistance genesSub-lineagesInvasive isolatesSerotype IIHost groupsExpansion 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 mutationVirulenceMetagenomics to improve infectious disease diagnostics in low- and middle-income countries
Jamiu A, Chaguza C. Metagenomics to improve infectious disease diagnostics in low- and middle-income countries. Nature Microbiology 2024, 9: 1150-1151. PMID: 38714760, DOI: 10.1038/s41564-024-01681-2.Peer-Reviewed Original ResearchDengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus
Vogels C, Hill V, Breban M, Chaguza C, Paul L, Sodeinde A, Taylor-Salmon E, Ott I, Petrone M, Dijk D, Jonges M, Welkers M, Locksmith T, Dong Y, Tarigopula N, Tekin O, Schmedes S, Bunch S, Cano N, Jaber R, Panzera C, Stryker I, Vergara J, Zimler R, Kopp E, Heberlein L, Herzog K, Fauver J, Morrison A, Michael S, Grubaugh N. DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus. BMC Genomics 2024, 25: 433. PMID: 38693476, PMCID: PMC11062901, DOI: 10.1186/s12864-024-10350-x.Peer-Reviewed Original ResearchConceptsAmplicon sequencing protocolsPrimer schemeSequencing protocolGenomic surveillanceDengue virus serotypesAmplicon sequencing workflowClinical specimensHigh genome coverageWhole-genome sequencingDengue virusVirus serotypesGenome coverageVirus stocksGenetic diversitySequencing instrumentsSequencing workflowGenotype VIDiverse serotypesSequence of samplesGenotype IVPrimersSurveillance of dengue virusSerotypesVirus copiesSerotype-specificTravel surveillance uncovers dengue virus dynamics and introductions in the Caribbean
Taylor-Salmon E, Hill V, Paul L, Koch R, Breban M, Chaguza C, Sodeinde A, Warren J, Bunch S, Cano N, Cone M, Eysoldt S, Garcia A, Gilles N, Hagy A, Heberlein L, Jaber R, Kassens E, Colarusso P, Davis A, Baudin S, Rico E, Mejía-Echeverri Á, Scott B, Stanek D, Zimler R, Muñoz-Jordán J, Santiago G, Adams L, Paz-Bailey G, Spillane M, Katebi V, Paulino-Ramírez R, Mueses S, Peguero A, Sánchez N, Norman F, Galán J, Huits R, Hamer D, Vogels C, Morrison A, Michael S, Grubaugh N. Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean. Nature Communications 2024, 15: 3508. PMID: 38664380, PMCID: PMC11045810, DOI: 10.1038/s41467-024-47774-8.Peer-Reviewed Original ResearchConceptsDengue virusDENV-3Rates of severe diseaseMosquito-borne viral diseasePublic health threatPattern of spreadSevere diseaseLocal surveillanceGenomic epidemiologyEpidemiological patternsVirus surveillanceSurveillanceHealth threatSerotypesDiseaseIncreased rateDengueViral diseasesVirusInfected travelersFrequent outbreaksIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusClonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction
Kalizang'oma A, Swarthout T, Mwalukomo T, Kamng'ona A, Brown C, Msefula J, Demetriou H, Chan J, Roalfe L, Obolski U, Lourenço J, Goldblatt D, Chaguza C, French N, Heyderman R. Clonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction. The Journal Of Infectious Diseases 2024, jiae040. PMID: 38530917, DOI: 10.1093/infdis/jiae040.Peer-Reviewed Original ResearchClonal expansionSequence typingAntimicrobial resistanceSusceptibility to opsonophagocytic killingWhole-genome sequencingStreptococcus pneumoniae serotype 3Serotype 3Post-PCV13 introductionNext-generation pneumococcal vaccinesPneumococcal conjugate vaccine introductionVaccine escapeConjugate vaccine introductionPneumococcal conjugate vaccineIncreased antimicrobial resistancePolysaccharide biosynthesisPhylogenetic reconstructionSequencing projectsLocus sequencesCapsule locusSequence clustersGenomic surveillanceOpsonophagocytic killingPhenotypic characteristicsVaccine introductionConjugate vaccine
2023
Development of an amplicon-based sequencing approach in response to the global emergence of mpox
Chen N, Chaguza C, Gagne L, Doucette M, Smole S, Buzby E, Hall J, Ash S, Harrington R, Cofsky S, Clancy S, Kapsak C, Sevinsky J, Libuit K, Park D, Hemarajata P, Garrigues J, Green N, Sierra-Patev S, Carpenter-Azevedo K, Huard R, Pearson C, Incekara K, Nishimura C, Huang J, Gagnon E, Reever E, Razeq J, Muyombwe A, Borges V, Ferreira R, Sobral D, Duarte S, Santos D, Vieira L, Gomes J, Aquino C, Savino I, Felton K, Bajwa M, Hayward N, Miller H, Naumann A, Allman R, Greer N, Fall A, Mostafa H, McHugh M, Maloney D, Dewar R, Kenicer J, Parker A, Mathers K, Wild J, Cotton S, Templeton K, Churchwell G, Lee P, Pedrosa M, McGruder B, Schmedes S, Plumb M, Wang X, Barcellos R, Godinho F, Salvato R, Ceniseros A, Breban M, Grubaugh N, Gallagher G, Vogels C. Development of an amplicon-based sequencing approach in response to the global emergence of mpox. PLOS Biology 2023, 21: e3002151. PMID: 37310918, PMCID: PMC10263305, DOI: 10.1371/journal.pbio.3002151.Peer-Reviewed Original ResearchConceptsPublic health laboratoriesHealth laboratoriesSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Monkeypox virusRespiratory syndrome coronavirus 2Ongoing coronavirus disease 2019 (COVID-19) pandemicAnatomical body sitesAtypical clinical presentationCoronavirus disease 2019 (COVID-19) pandemicSyndrome coronavirus 2Course of infectionDisease 2019 pandemicRapid outbreak responseWhole-genome sequencingHuman monkeypox virusCT valuesClinical presentationViral loadCoronavirus 2Viral DNA concentrationsPathogen whole-genome sequencingZika virusClinical specimensBody sitesComparative whole genome analysis reveals re-emergence of human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi
Mhango C, Banda A, Chinyama E, Mandolo J, Kumwenda O, Malamba-Banda C, Barnes K, Kumwenda B, Jambo K, Donato C, Esona M, Mwangi P, Steele A, Iturriza-Gomara M, Cunliffe N, Ndze V, Kamng'ona A, Dennis F, Nyaga M, Chaguza C, Jere K. Comparative whole genome analysis reveals re-emergence of human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi. Virus Evolution 2023, 9: vead030. PMID: 37305707, PMCID: PMC10256189, DOI: 10.1093/ve/vead030.Peer-Reviewed Original ResearchBackbone genesComparative whole genome analysisFurther genomic analysisGenotype constellationRecent common ancestorWhole genome sequencesWhole-genome analysisAmino acid substitutionsCommon ancestorPhylogenetic treeGenome sequenceGenome analysisGenomic analysisInterspecies reassortmentGenetic similarityGenome segmentsNSP2 geneAcid substitutionsReassortment eventsAcid segmentGenesVP4 proteinG3 rotavirusesG3 strainsHuman WaEnhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpressionToward a global virus genomic surveillance network
Hill V, Githinji G, Vogels C, Bento A, Chaguza C, Carrington C, Grubaugh N. Toward a global virus genomic surveillance network. Cell Host & Microbe 2023, 31: 861-873. PMID: 36921604, PMCID: PMC9986120, DOI: 10.1016/j.chom.2023.03.003.Peer-Reviewed Original ResearchAge-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
Filardi B, Monteiro V, Schwartzmann P, do Prado Martins V, Zucca L, Baiocchi G, Malik A, Silva J, Hahn A, Chen N, Pham K, Pérez-Then E, Miric M, Brache V, Cochon L, Larocca R, Della Rosa Mendez R, Silveira D, Pinto A, Croda J, Yildirim I, Omer S, Ko A, Vermund S, Grubaugh N, Iwasaki A, Lucas C, Initiative Y, Vogels C, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W. Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose. Science Translational Medicine 2023, 15: eade6023. PMID: 36791210, DOI: 10.1126/scitranslmed.ade6023.Peer-Reviewed Original ResearchConceptsBooster doseAntibody responseNeutralization titersVirus-specific IgG titersOlder adultsAntiviral humoral immunityPlasma antibody responsesHigh-risk populationSARS-CoV-2 spikeYears of ageAge-dependent impairmentHeterologous regimensBooster dosesBooster vaccineCoronaVac vaccineIgG titersProtective immunityHumoral immunityHumoral responseCoronaVacOmicron waveBooster strategyAge groupsEarly controlVaccine