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 pipelineApicoplastKalihinolTraffickingMalariaTwo 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
Functional 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 assays
2016
Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
Dankwa S, Lim C, Bei AK, Jiang RH, Abshire JR, Patel SD, Goldberg JM, Moreno Y, Kono M, Niles JC, Duraisingh MT. Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite. Nature Communications 2016, 7: 11187. PMID: 27041489, PMCID: PMC4822025, DOI: 10.1038/ncomms11187.Peer-Reviewed Original ResearchConceptsInvasion ligandsSialic acid-independent pathwaysHuman RBCsZoonotic malaria parasiteAbsence of Neu5GcPlasmodium knowlesiMalaria parasitesCell surface receptorsN-glycolylneuraminic acidZoonotic parasitesSialic acid variantsSurface receptorsRBCsReceptorsNeu5GcMacaquesInvasionParasitesCMAHAcetylneuraminic acidAcid variantsHumansMalariaKnowlesi
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 stageAnalysis 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
Inhibitory 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
2010
Functional diversification between two related Plasmodium falciparum merozoite invasion ligands is determined by changes in the cytoplasmic domain
Dvorin JD, Bei AK, Coleman BI, Duraisingh MT. Functional diversification between two related Plasmodium falciparum merozoite invasion ligands is determined by changes in the cytoplasmic domain. Molecular Microbiology 2010, 75: 990-1006. PMID: 20487292, PMCID: PMC3627358, DOI: 10.1111/j.1365-2958.2009.07040.x.Peer-Reviewed Original ResearchConceptsCytoplasmic domainFunctional diversificationInvasion pathwaysMulti-gene familyDifferent erythrocyte receptorsAmino acid regionAlternative invasion pathwaysN-terminal amino acidsGenomic regionsProtein homologueTransmembrane domainTransmembrane regionPfRh proteinsErythrocyte receptorEfficient invasionAcid regionInvasive merozoitesHost erythrocytePfRh2bAmino acidsPfRh2aPathway utilizationApical surfaceInvasion ligandsEctodomain
2009
Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates of Plasmodium falciparum
LANTOS PM, AHOUIDI AD, BEI AK, JENNINGS CV, SARR O, NDIR O, WIRTH DF, MBOUP S, DURAISINGH MT. Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates of Plasmodium falciparum. Parasitology 2009, 136: 1-9. PMID: 19126266, DOI: 10.1017/s0031182008005167.Peer-Reviewed Original ResearchConceptsErythrocyte receptorSialic acid-independent invasionBlood group O patientsDifferent erythrocyte receptorsGroup O patientsSenegalese isolatesParasite multiplication ratePlasmodium falciparum parasitesMultiple ligand-receptor interactionsO patientsFalciparum parasitesLarge sequence deletionsVariant expression levelParasite isolatesPlasmodium falciparumErythrocyte invasionSelectivity indexReceptorsExpression levelsMajor polymorphismsInvasionInvasion pathwaysPossible determinantsParasitesHuman erythrocytes
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