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 ResearchConceptsP. 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 approach
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
2017
High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations
Ndiaye YD, Diédhiou CK, Bei AK, Dieye B, Mbaye A, Mze NP, Daniels RF, Ndiaye IM, Déme AB, Gaye A, Sy M, Ndiaye T, Badiane AS, Ndiaye M, Premji Z, Wirth DF, Mboup S, Krogstad D, Volkman SK, Ahouidi AD, Ndiaye D. High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations. Malaria Journal 2017, 16: 153. PMID: 28420422, PMCID: PMC5395743, DOI: 10.1186/s12936-017-1811-2.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildChild, PreschoolDihydropteroate SynthaseDrug ResistanceGenotypeGenotyping TechniquesHumansMalaria, FalciparumMolecular Diagnostic TechniquesPlasmodiumPoint-of-Care SystemsPolymerase Chain ReactionPolymorphism, Restriction Fragment LengthSenegalTanzaniaTetrahydrofolate DehydrogenaseTransition TemperatureYoung AdultConceptsMalaria endemic sitesDrug resistanceHigh prevalenceUncomplicated Plasmodium falciparum malariaPolymerase chain reaction-restriction fragment length polymorphism methodologyAnti-malarial drug usePlasmodium falciparum malariaEndemic sitesEmergence of resistanceMultiplicity of infectionFalciparum malariaFragment length polymorphism methodologyDHFR mutationsBlood samplesMalaria endemicityPCR-RFLP genotypingPCR/RFLPTreatment policyCodon 540Drug usePlasmodium populationsMixed allelesEarly detectionCodons 51Mixed infectionsGenetic 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 ResearchConceptsVaccine candidatesBlood-stage vaccine candidatePromising vaccine targetPlasmodium falciparum merozoitesRelevant evidence baseFalciparum merozoitesVaccine targetsEvidence baseErythrocyte invasionStandardized assaysParasite survivalInvasion phenotypeInvasion studiesTrue extentField isolatesInvasionMost studiesLigands differsMeasuring 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 genotypesAnalysis 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 ResearchConceptsMerozoite 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 strainsVaccine
2012
SNP Genotyping Identifies New Signatures of Selection in a Deep Sample of West African Plasmodium falciparum Malaria Parasites
Amambua-Ngwa A, Park DJ, Volkman SK, Barnes KG, Bei AK, Lukens AK, Sene P, Van Tyne D, Ndiaye D, Wirth DF, Conway DJ, Neafsey DE, Schaffner SF. SNP Genotyping Identifies New Signatures of Selection in a Deep Sample of West African Plasmodium falciparum Malaria Parasites. Molecular Biology And Evolution 2012, 29: 3249-3253. PMID: 22688945, PMCID: PMC3472499, DOI: 10.1093/molbev/mss151.Peer-Reviewed Original ResearchConceptsHigh-density single nucleotide polymorphism arraysRecent selective sweepLocal selection pressuresSignals of selectionDrug resistance lociSingle nucleotide polymorphism arrayHaplotype-based testsPlasmodium falciparum malaria parasitesSelective sweepsResistance lociGenetic diversityGenomic regionsRecent selectionGenomic analysisSelection signalsPositive selectionSelection pressureFalciparum malaria parasitesPolymorphism arrayAntigenic lociMalaria parasitesMosquito vectorsEndemic populationsLociParasites
2010
In Vitro Genetic Analysis of an Erythrocyte Determinant of Malaria Infection
Bei AK, Brugnara C, Duraisingh MT. In Vitro Genetic Analysis of an Erythrocyte Determinant of Malaria Infection. The Journal Of Infectious Diseases 2010, 202: 1722-1727. PMID: 20958212, PMCID: PMC3107553, DOI: 10.1086/657157.Peer-Reviewed Original ResearchMeSH KeywordsCoculture TechniquesErythrocytesFlow CytometryGlycophorinsHost-Parasite InteractionsHumansMalaria, FalciparumPlasmodium falciparumConceptsGenetic analysisErythrocyte determinantsSystematic functional analysisDirect genetic analysisErythrocyte biologyInvasion of erythrocytesIsogenic backgroundP. falciparum invasionGene expressionFunctional analysisParasite invasionObligatory stepLentiviral transductionHost receptorsGlycophorin ALife cyclePlasmodium falciparumCulture systemInvasionMalaria infectionUnambiguous identificationTransductionBiologyParasitesErythrocytesA flow cytometry‐based assay for measuring invasion of red blood cells by Plasmodium falciparum
Bei AK, DeSimone TM, Badiane AS, Ahouidi AD, Dieye T, Ndiaye D, Sarr O, Ndir O, Mboup S, Duraisingh MT. A flow cytometry‐based assay for measuring invasion of red blood cells by Plasmodium falciparum. American Journal Of Hematology 2010, 85: 234-237. PMID: 20196166, PMCID: PMC3089760, DOI: 10.1002/ajh.21642.Peer-Reviewed Original ResearchConceptsParasite invasionMalaria parasite Plasmodium falciparumParasite Plasmodium falciparumPlasmodium falciparumFlow cytometry-based assayParasite multiplication rateFlow cytometry-based methodParasite developmentCytometry-based assayCytometry-based methodRed blood cellsDisease severityDye SYBR Green IRing stageVariable invasionMultiplication rateBlood cellsInvasionSYBR Green IHuman erythrocytesFalciparumGreen IImportant determinantErythrocytesParasitemia
2007
Molecular Analysis of Erythrocyte Invasion in Plasmodium falciparum Isolates from Senegal
Jennings CV, Ahouidi AD, Zilversmit M, Bei AK, Rayner J, Sarr O, Ndir O, Wirth DF, Mboup S, Duraisingh MT. Molecular Analysis of Erythrocyte Invasion in Plasmodium falciparum Isolates from Senegal. Infection And Immunity 2007, 75: 3531-3538. PMID: 17470537, PMCID: PMC1932937, DOI: 10.1128/iai.00122-07.Peer-Reviewed Original ResearchConceptsInvasion pathwaysSequence polymorphismsMolecular analysisDistinct invasion pathwaysC-terminal regionMalaria parasitesSpecific sequence variantsGene amplificationHuman malaria parasiteLigand-receptor interactionsExpression polymorphismsRepeat regionProtein expression levelsSequence deletionsHomolog familyMultiple ligand-receptor interactionsLarge sequence deletionsSequence variantsSignificant sequence polymorphismErythrocyte invasionErythrocyte receptorP. falciparum parasitesExpression levelsPfRh1Low transmission areasVariant merozoite protein expression is associated with erythrocyte invasion phenotypes in Plasmodium falciparum isolates from Tanzania
Bei AK, Membi CD, Rayner JC, Mubi M, Ngasala B, Sultan AA, Premji Z, Duraisingh MT. Variant merozoite protein expression is associated with erythrocyte invasion phenotypes in Plasmodium falciparum isolates from Tanzania. Molecular And Biochemical Parasitology 2007, 153: 66-71. PMID: 17303262, DOI: 10.1016/j.molbiopara.2007.01.007.Peer-Reviewed Original Research