2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimalarialsApicoplastsDisease Models, AnimalDiterpenesDrug ResistanceHumansMalaria, FalciparumMiceMutationPlasmodium falciparumProtozoan ProteinsConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalariaUnderstanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory
Nahid D, Coffey K, Bei A, Cordy R. Understanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory. PLOS Pathogens 2024, 20: e1012514. PMID: 39298535, PMCID: PMC11412506, DOI: 10.1371/journal.ppat.1012514.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErythrocytesHumansLife Cycle StagesMalaria, FalciparumOxidative StressOxygenPlasmodium falciparumReactive Oxygen SpeciesConceptsRed blood cellsIntraerythrocytic developmentReactive oxygen speciesPlasmodium falciparum blood stagesMultiple organ systemsP. falciparum mitochondrionStatus of hemoglobinBlood stagesPlasmodium falciparumReactive oxygen species productionO2-sensing mechanismIn vitro experimentsPlasmodiumBlood cellsOxygenation statusOrgan systemsFunctional changesParasite growthOxidative stressOxygen tensionMosquito hostCulture systemDeep tissuesOxygen speciesTwo decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time
Ndiaye Y, Wong W, Thwing J, Schaffner S, Brenneman K, Tine A, Diallo M, Deme A, Sy M, Bei A, Thiaw A, Daniels R, Ndiaye T, Gaye A, Ndiaye I, Toure M, Gadiaga N, Sene A, Sow D, Garba M, Yade M, Dieye B, Diongue K, Zoumarou D, Ndiaye A, Gomis J, Fall F, Ndiop M, Diallo I, Sene D, Macinnis B, Seck M, Ndiaye M, Ngom B, Diedhiou Y, Mbaye A, Ndiaye L, Sy N, Badiane A, Hartl D, Wirth D, Volkman S, Ndiaye D. Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time. Malaria Journal 2024, 23: 205. PMID: 38982475, PMCID: PMC11234717, DOI: 10.1186/s12936-024-05024-8.Peer-Reviewed Original ResearchConceptsPfcrt K76TArtemisinin-based combination therapyPfdhps A437GSeasonal malaria chemopreventionK76TDrug resistance mutationsMolecular surveillanceA437GSulfadoxine-pyrimethamineArtesunate-amodiaquineSingle nucleotide polymorphismsDrug resistance markersResistance mutationsEfficacy of artesunate-amodiaquineWithdrawal of chloroquineMalaria control effortsP. falciparum parasitesResistance markersCombination of single nucleotide polymorphismsParasite drug resistanceWhole-genome sequencingAQ resistanceHaplotype-based analysisMalaria chemopreventionCombination therapy
2023
Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017
Yade M, Dièye B, Coppée R, Mbaye A, Diallo M, Diongue K, Bailly J, Mama A, Fall A, Thiaw A, Ndiaye I, Ndiaye T, Gaye A, Tine A, Diédhiou Y, Mbaye A, Doderer-Lang C, Garba M, Bei A, Ménard D, Ndiaye D. Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017. Malaria Journal 2023, 22: 167. PMID: 37237307, PMCID: PMC10223908, DOI: 10.1186/s12936-023-04588-1.Peer-Reviewed Original ResearchConceptsRing-stage survival assayART resistancePlasmodium falciparum isolatesMost malaria deathsLong-term useCurative treatmentCombination therapyMalaria deathsMinor variantsFalciparum isolatesPfkelch13 geneSurvival assaysParasite susceptibilityResultsAll samplesPfKelch13Spread of parasitesSaharan AfricaExMain determinantsIsolatesTherapySusceptibilityDeep sequencing approachTracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study
Ehrlich H, Somé A, Bazié T, Ebou C, Dembélé E, Balma R, Goodwin J, Wade M, Bei A, Ouédraogo J, Foy B, Dabiré R, Parikh S. Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study. The Lancet Microbe 2023, 4: e461-e469. PMID: 37086737, PMCID: PMC10365133, DOI: 10.1016/s2666-5247(23)00063-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimalarialsCross-Sectional StudiesCulicidaeFolic Acid AntagonistsHumansPlasmodium falciparumPolymerase Chain ReactionConceptsMosquito blood mealsAntimalarial drug resistanceSurvey 3Blood-fed mosquitoesBlood samplesSurvey 1Survey 2Blood mealDrug resistanceUltrasensitive quantitative PCRHuman blood samplesCross-sectional studyMargin of equivalenceStrong surveillance systemCross-sectional surveySupplementary Materials sectionMarker of clonalityPragmatic thresholdAntimalarial resistanceDrug susceptibilityInfectious diseasesPlasmodium falciparumNational InstituteTolerabilityMaterial section
2022
Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5
Mangou K, Moore A, Thiam L, Ba A, Orfanó A, Desamours I, Ndegwa D, Goodwin J, Guo Y, Sheng Z, Patel S, Diallo F, Sene S, Pouye M, Faye A, Thiam A, Nunez V, Diagne C, Sadio B, Shapiro L, Faye O, Mbengue A, Bei A. Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5. Scientific Reports 2022, 12: 19403. PMID: 36371450, PMCID: PMC9653458, DOI: 10.1038/s41598-022-23929-9.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ProtozoanAntigens, ProtozoanCarrier ProteinsHumansMalaria VaccinesMalaria, FalciparumPlasmodium falciparumProtozoan ProteinsConceptsImmune evasionSingle nucleotide polymorphismsPopulation prevalenceVaccine-induced protective immunityP. falciparum positive samplesFalciparum positive samplesPlasmodium falciparum antigensMalaria vaccine candidateNovel single nucleotide polymorphismsInhibitory monoclonal antibodiesProtective immunityFalciparum antigensMalaria deathsEffective vaccineEfficacious vaccineVaccine candidatesPfRH5Infected individualsVaccine targetsMonoclonal antibodiesLow overall frequencyReceptor bindingNovel genetic variantsVaccineOverall frequency
2018
De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria
Redmond SN, MacInnis BM, Bopp S, Bei AK, Ndiaye D, Hartl DL, Wirth DF, Volkman SK, Neafsey DE. De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria. Molecular Biology And Evolution 2018, 35: 1678-1689. PMID: 29722884, PMCID: PMC5995194, DOI: 10.1093/molbev/msy059.Peer-Reviewed Original ResearchConceptsDe novo mutationsEvolutionary ratesSlow evolutionary rateNovo mutationsComplex life cycleSlow generation timeLow-complexity regionsGenomic regionsLarge genomesGenomic epidemiology approachReintroduction scenariosCombination of sequencingP. falciparumViral speciesMutation rateClonal lineagesGenomeMutation studiesLibrary preparationIdentical parasitesGeneration timeBacterial pathogensMalaria parasitesMutationsGenomic epidemiology
2017
Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes
Dankwa S, Chaand M, Kanjee U, Jiang RHY, Nobre LV, Goldberg JM, Bei AK, Moechtar MA, Grüring C, Ahouidi AD, Ndiaye D, Dieye TN, Mboup S, Weekes MP, Duraisingh MT. Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes. Infection And Immunity 2017, 85: 10.1128/iai.00074-17. PMID: 28760933, PMCID: PMC5607420, DOI: 10.1128/iai.00074-17.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyErythrocytesGlycophorinsHumansLigandsPlasmodium falciparumProtein BindingProteomicsReceptors, Cell SurfaceConceptsInvasion pathwaysGlycophorin CGlycophorin BExpression levelsShort hairpin RNA transductionLigand-receptor interactionsErythroid progenitor cellsKnockout linesGenetic evidenceBioinformatics analysisKnockdown cellsProteomic profilingTranscript levelsMultiple proteinsHuman erythrocytesExtensive variationParasite invasionProgenitor cellsInvasion ligandsB expression levelsLaboratory strainsGPC receptorsCulture-adapted strainsPathwayReceptor usageFunctional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen
Bei AK, Ahouidi AD, Dvorin JD, Miura K, Diouf A, Ndiaye D, Premji Z, Diakite M, Mboup S, Long CA, Duraisingh MT. Functional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen. The Journal Of Infectious Diseases 2017, 216: 267-275. PMID: 28605544, PMCID: PMC5853457, DOI: 10.1093/infdis/jix280.Peer-Reviewed Original ResearchConceptsInhibitory immune responsesVaccine candidate antigenImmune responseTransgenic parasite linesMalaria-endemic regionsReticulocyte-binding protein homologuesMalaria vaccine candidateParasite linesWild-type controlsTotal IgGHumoral responseMalaria antigensAntibody responseVaccine candidatesCandidate antigensMalaria endemicityGrowth inhibition assaysInvasion ligandsAntigenic specificityImmunogenic domainsSpecific antibodiesEndemic sitesAntigenStandardized toolsInhibition assaysGenetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal
Wong W, Griggs AD, Daniels RF, Schaffner SF, Ndiaye D, Bei AK, Deme AB, MacInnis B, Volkman SK, Hartl DL, Neafsey DE, Wirth DF. Genetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal. Genome Medicine 2017, 9: 5. PMID: 28118860, PMCID: PMC5260019, DOI: 10.1186/s13073-017-0398-0.Peer-Reviewed Original ResearchMeSH KeywordsGenetic VariationGenome, ProtozoanHumansMalaria, FalciparumMarkov ChainsModels, GeneticPlasmodium falciparumSenegalConceptsPolygenomic infectionsRelatedness of strainsMalaria elimination activitiesPlasmodium falciparum parasitesPublic health interventionsEpidemiology modelFalciparum parasitesHealth interventionsDrug resistanceInfectionParasite populationsConclusionsOur findingsCotransmissionSuperinfection modelElimination activitiesTransmission intensityGenetic relatedness analysisGenetic profileInterventionParasitesMajor contributorPatientsPopulationSuperinfectionThiès
2015
Malaria Vaccine Development: Focusing Field Erythrocyte Invasion Studies on Phenotypic Diversity The West African Merozoite Invasion Network (WAMIN)
: T, Ahouidi AD, Amambua-Ngwa A, Awandare GA, Bei AK, Conway DJ, Diakite M, Duraisingh MT, Rayner JC, Zenonos ZA. Malaria Vaccine Development: Focusing Field Erythrocyte Invasion Studies on Phenotypic Diversity The West African Merozoite Invasion Network (WAMIN). Trends In Parasitology 2015, 32: 274-283. PMID: 26725306, PMCID: PMC7021314, DOI: 10.1016/j.pt.2015.11.009.Peer-Reviewed Original ResearchMeSH KeywordsAfrica, WesternAnimalsCooperative BehaviorErythrocytesGenetic VariationHumansMalaria VaccinesMalaria, FalciparumPhenotypePlasmodium falciparumResearchConceptsVaccine candidatesBlood-stage vaccine candidatePromising vaccine targetPlasmodium falciparum merozoitesRelevant evidence baseFalciparum merozoitesVaccine targetsEvidence baseErythrocyte invasionStandardized assaysParasite survivalInvasion phenotypeInvasion studiesTrue extentField isolatesInvasionMost studiesLigands differsThe Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity
Tubman VN, Mejia P, Shmukler BE, Bei AK, Alper SL, Mitchell JR, Brugnara C, Duraisingh MT. The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity. Antimicrobial Agents And Chemotherapy 2015, 60: 613-616. PMID: 26459896, PMCID: PMC4704178, DOI: 10.1128/aac.01668-15.Peer-Reviewed Original ResearchConceptsGardos channel inhibitorChannel inhibitorsSickle cell diseaseC57BL/6 miceClinical trialsCell diseaseAntimalarial developmentPlasmodium growthErythrocyte dehydrationGardos channelSenicapocBlood stagesBiochemical profileAntimalarial activityPrimate plasmodiaVitro growthInhibitorsPatientsParasitemiaBlockadeDiseaseMiceTrialsMeasuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry
Bei AK, Duraisingh MT. Measuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry. Methods In Molecular Biology 2015, 1325: 167-186. PMID: 26450388, DOI: 10.1007/978-1-4939-2815-6_14.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ProtozoanErythrocytesFlow CytometryHumansMalaria, FalciparumPlasmodium falciparumSchizontsConceptsPlasmodium falciparum merozoite invasionParasite multiplication rateErythrocyte invasion phenotypesInvasion of erythrocytesFlow cytometry methodVaccine mechanismDisease severityInvasion inhibitionEx vivoFlow cytometryMerozoite invasionCytometry methodRing stageInvasion phenotypeInvasionResearch settingsVivoImportant determinantLow levelsAlternative pathwayParasitesParasitemia
2014
Immune Characterization of Plasmodium falciparum Parasites with a Shared Genetic Signature in a Region of Decreasing Transmission
Bei AK, Diouf A, Miura K, Larremore DB, Ribacke U, Tullo G, Moss EL, Neafsey DE, Daniels RF, Zeituni AE, Nosamiefan I, Volkman SK, Ahouidi AD, Ndiaye D, Dieye T, Mboup S, Buckee CO, Long CA, Wirth DF. Immune Characterization of Plasmodium falciparum Parasites with a Shared Genetic Signature in a Region of Decreasing Transmission. Infection And Immunity 2014, 83: 276-285. PMID: 25368109, PMCID: PMC4288878, DOI: 10.1128/iai.01979-14.Peer-Reviewed Original ResearchConceptsQuantitative reverse transcription PCRCommon genetic signatureSurface antigenClinical isolatesVar genesPlasmodium falciparum parasite populationsVariant surface antigensPlasmodium falciparum parasitesParasite-infected erythrocytesImmune characterizationMajor variant surface antigenSpecific parasite genotypesReverse transcription-PCRImmune responseFalciparum parasitesImmune recognitionMalaria transmissionVar transcriptsInfected erythrocytesParasite growthParasite clonesTranscription-PCRAntibodiesParasite correlatesParasite genotypesSTEVOR Is a Plasmodium falciparum Erythrocyte Binding Protein that Mediates Merozoite Invasion and Rosetting
Niang M, Bei AK, Madnani KG, Pelly S, Dankwa S, Kanjee U, Gunalan K, Amaladoss A, Yeo KP, Bob NS, Malleret B, Duraisingh MT, Preiser PR. STEVOR Is a Plasmodium falciparum Erythrocyte Binding Protein that Mediates Merozoite Invasion and Rosetting. Cell Host & Microbe 2014, 16: 81-93. PMID: 25011110, PMCID: PMC4382205, DOI: 10.1016/j.chom.2014.06.004.Peer-Reviewed Original ResearchConceptsMerozoite invasionFalciparum erythrocyte membrane protein 1P. falciparum erythrocyte membrane protein 1Erythrocyte membrane protein 1Variant surface antigensErythrocyte binding proteinInfected erythrocyte surfaceErythrocyte-binding proteinsMembrane protein 1STEVOR expressionMalaria pathogenesisRed blood cell surfaceImmune evasionSurface antigenUninfected RBCsBlood cell surfaceGlycophorin CInfected RBCsErythrocyte surfaceParasite infectionProtein 1Invasive merozoitesForm rosettesSTEVORSchizont stageAn Adjustable Gas-Mixing Device to Increase Feasibility of In Vitro Culture of Plasmodium falciparum Parasites in the Field
Bei AK, Patel SD, Volkman SK, Ahouidi AD, Ndiaye D, Mboup S, Wirth DF. An Adjustable Gas-Mixing Device to Increase Feasibility of In Vitro Culture of Plasmodium falciparum Parasites in the Field. PLOS ONE 2014, 9: e90928. PMID: 24603696, PMCID: PMC3946284, DOI: 10.1371/journal.pone.0090928.Peer-Reviewed Original ResearchMeSH KeywordsAutomation, LaboratoryCarbon DioxideErythrocytesHumansNitrogenOxygenPlasmodium falciparumPrimary Cell CultureAnalysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests
Deme AB, Park DJ, Bei AK, Sarr O, Badiane AS, Gueye Pel H, Ahouidi A, Ndir O, Mboup S, Wirth DF, Ndiaye D, Volkman SK. Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests. Malaria Journal 2014, 13: 34. PMID: 24472178, PMCID: PMC3913323, DOI: 10.1186/1475-2875-13-34.Peer-Reviewed Original ResearchConceptsGenetic diversityNucleotide diversityNon-synonymous nucleotide diversityRepeat length polymorphismAmino acid repeatsPfhrp2 geneLength polymorphismExtent of polymorphismEssential genesParasite ecologyAcid repeatsDiversity surveysParasite proteinsBp regionGenesProtein 2Polymorphic genesRepeatsDiversityHistidine-rich protein 2PfHRP2 antigenSenegalese National Malaria Control ProgrammeHRP2 detectionAntigen diversityPlasmodium falciparum
2013
Plasmodium falciparum Merozoite Surface Antigen, PfRH5, Elicits Detectable Levels of Invasion-Inhibiting Antibodies in Humans
Patel SD, Ahouidi AD, Bei AK, Dieye TN, Mboup S, Harrison SC, Duraisingh MT. Plasmodium falciparum Merozoite Surface Antigen, PfRH5, Elicits Detectable Levels of Invasion-Inhibiting Antibodies in Humans. The Journal Of Infectious Diseases 2013, 208: 1679-1687. PMID: 23904294, PMCID: PMC3805239, DOI: 10.1093/infdis/jit385.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ProtozoanAntigens, ProtozoanCarrier ProteinsHumansImmunoglobulin GMalaria, FalciparumMerozoitesPlasmodium falciparumRecombinant ProteinsConceptsMerozoite surface antigenSurface antigenPlasmodium falciparum merozoite surface antigenMulti-subunit vaccineMillions of infectionsIntracellular protozoan parasiteInvasion inhibition assaysSubstantial morbidityClinical isolatesP. falciparumBlood stagesPlasmodium falciparumNatural infectionAntibodiesPfRH5Protozoan parasiteDetectable levelsInhibition assaysInfectionAntigenFalciparumRecombinant formMorbidityLaboratory strainsVaccineInhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway
Badiane AS, Bei AK, Ahouidi AD, Patel SD, Salinas N, Ndiaye D, Sarr O, Ndir O, Tolia NH, Mboup S, Duraisingh MT. Inhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway. MSphere 2013, 20: 1238-1245. PMID: 23761656, PMCID: PMC3754519, DOI: 10.1128/cvi.00135-13.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayEBA-175Human antibodiesAffinity-purified human antibodiesBlood-stage vaccine candidateParasite strainsSialic acid-dependent mannerParasite invasionPresence of antibodiesErythrocyte-binding domainMultiple ligand-receptor interactionsEx vivo assaysPooled patient plasmaSenegalese parasitesAlternative invasion pathwaysHumoral responseVaccine candidatesPatient plasmaSenegalese patientsLigand-receptor interactionsClinical isolatesInvasion inhibitionVaccine designEx vivoFunctional inhibition
2012
Nuclear Repositioning Precedes Promoter Accessibility and Is Linked to the Switching Frequency of a Plasmodium falciparum Invasion Gene
Coleman BI, Ribacke U, Manary M, Bei AK, Winzeler EA, Wirth DF, Duraisingh MT. Nuclear Repositioning Precedes Promoter Accessibility and Is Linked to the Switching Frequency of a Plasmodium falciparum Invasion Gene. Cell Host & Microbe 2012, 12: 739-750. PMID: 23245319, PMCID: PMC4066821, DOI: 10.1016/j.chom.2012.11.004.Peer-Reviewed Original Research