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 diseaseWithin-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
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 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 virus
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 sitesEnhanced 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 controlVaccineAccelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection
Chaguza C, Hahn A, Petrone M, Zhou S, Ferguson D, Breban M, Pham K, Peña-Hernández M, Castaldi C, Hill V, Initiative Y, Billig K, Earnest R, Fauver J, Kalinch C, Kerantzas N, Koch T, De Kumar B, Landry M, Ott I, Peaper D, Tikhonova I, Vogels C, Schulz W, Swanstrom R, Roberts S, Grubaugh N. Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection. Cell Reports Medicine 2023, 4: 100943. PMID: 36791724, PMCID: PMC9906997, DOI: 10.1016/j.xcrm.2023.100943.Peer-Reviewed Original ResearchConceptsChronic infectionEvolutionary ratesGenetic diversityIntrahost evolutionDistinct genotypesHigher viral genome copiesVirus evolutionary ratesSARS-CoV-2 evolutionUntreated chronic infectionAdvantageous mutationsNucleotide substitutionsViral genome copiesDivergent variantsInfection hypothesisVariant emergenceViral populationsInfectious virusInfectionHallmark changesGenome copiesDifferent genotypesDiversityGenotypesTemporal dynamicsEvolution
2022
Novel Multilocus Sequence Typing and Global Sequence Clustering Schemes for Characterizing the Population Diversity of Streptococcus mitis
Kalizang’oma A, Kwambana-Adams B, Chan J, Viswanath A, Gori A, Richard D, Jolley K, Lees J, Goldblatt D, Beleza S, Bentley S, Heyderman R, Chaguza C. Novel Multilocus Sequence Typing and Global Sequence Clustering Schemes for Characterizing the Population Diversity of Streptococcus mitis. Journal Of Clinical Microbiology 2022, 61: e00802-22. PMID: 36515506, PMCID: PMC9879099, DOI: 10.1128/jcm.00802-22.Peer-Reviewed Original ResearchConceptsSequence clustersPathogenic streptococcal speciesMultilocus sequence typing (MLST) schemePopulation diversitySingle-nucleotide polymorphism distancesSequence typesSequence typing schemeUnique sequence typesGenetic diversityPopulation structureBacterial population diversityMolecular typing toolsS. mitisHousekeeping genesSequence fragmentsMLST schemeDiversityOpportunistic pathogenStreptococcus mitisStreptococcal speciesTyping toolSpeciesNew insightsTyping schemeMultilocus sequence typingDaily Rapid Antigen Exit Testing to Tailor University COVID-19 Isolation Policy - Volume 28, Number 12—December 2022 - Emerging Infectious Diseases journal - CDC
Earnest R, Chen C, Chaguza C, Hahn A, Grubaugh N, Wilson M, . Daily Rapid Antigen Exit Testing to Tailor University COVID-19 Isolation Policy - Volume 28, Number 12—December 2022 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2022, 28: 2455-2462. PMID: 36417936, PMCID: PMC9707582, DOI: 10.3201/eid2812.220969.Peer-Reviewed Original ResearchPneumococcal 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 ResearchConceptsAntimicrobial treatmentAbsence of treatmentMultidrug-resistant bacteriumNasopharyngeal samplesElevated riskGold standard methodTreatment dataStreptococcus pneumoniaePersistent colonizationPneumococcal populationGenomic surveillanceInter-strain competitionTreatmentDeep sequencingInfantsResistant lineagesElevated ratesBacterial pathogensFirst yearMothersSensitive bacteriaTransmission chainSurveillanceSusceptible lineagesPathogensEvaluation of Dried Blood and Cerebrospinal Fluid Filter Paper Spots for Storing and Transporting Clinical Material for the Molecular Diagnosis of Invasive Meningococcal Disease
Kwambana-Adams B, Clark S, Tay N, Agbla S, Chaguza C, Kagucia E, Borrow R, Heyderman R. Evaluation of Dried Blood and Cerebrospinal Fluid Filter Paper Spots for Storing and Transporting Clinical Material for the Molecular Diagnosis of Invasive Meningococcal Disease. International Journal Of Molecular Sciences 2022, 23: 11879. PMID: 36233182, PMCID: PMC9569512, DOI: 10.3390/ijms231911879.Peer-Reviewed Original ResearchConceptsInvasive meningococcal diseaseMeningococcal diseaseNeisseria meningitidis infectionResource-limited settingsLow-resource settingsFilter paper spotsMeningococcal infectionReal-time PCRCerebrospinal fluidClinical specimensSubset of specimensBlood spotsSpot assayAntimicrobial resistanceBloodMolecular diagnosisClonal complexesClinical materialPaper spotsWhole-genome sequencingDBSInfectionSequence typesDiseaseDiagnosisComparative 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 ResearchConceptsGenomic 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 ResearchRapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med 2022, 3: 325-334.e4. PMID: 35399324, PMCID: PMC8983481, DOI: 10.1016/j.medj.2022.03.010.Peer-Reviewed Original ResearchConceptsSpike gene target failureSARS-CoV-2 Omicron variantPositivity rateOmicron variantOmicron infectionVaccine dosesVaccine-induced immunityNumber of dosesTest positivity rateOdds of infectionSARS-CoV-2Significant reductionDominant Delta variantUnvaccinated personsVaccination statusHigher oddsDelta variantInfectionVaccine manufacturersDisease controlVirus copiesDosesPCR testOddsTarget failureA 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 ResearchConceptsCommensal 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 bacteria