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 ResearchConceptsRed 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 species
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 ResearchConceptsMosquito 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
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
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 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 ResearchConceptsPlasmodium 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
STEVOR 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 stage
2013
Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans
Lim C, Hansen E, DeSimone TM, Moreno Y, Junker K, Bei A, Brugnara C, Buckee CO, Duraisingh MT. Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans. Nature Communications 2013, 4: 1638. PMID: 23535659, PMCID: PMC3762474, DOI: 10.1038/ncomms2612.Peer-Reviewed Original ResearchConceptsRed blood cellsParasite densityP. knowlesiHuman bloodPlasmodium falciparum infectionMalaria parasite Plasmodium knowlesiYoung red blood cellsZoonotic malaria parasiteHigh parasite densityOld red blood cellsFalciparum infectionClinical infectionSevere diseaseWide age rangeNormal human bloodPlasmodium knowlesiMalaria parasitesBlood cellsImportant zoonosisAge rangeInfectionBloodKnowlesiYoung cellsCulture system
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
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
Trypanosoma cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection
Chessler AD, Unnikrishnan M, Bei AK, Daily JP, Burleigh BA. Trypanosoma cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection. The Journal Of Immunology 2009, 182: 2288-2296. PMID: 19201883, DOI: 10.4049/jimmunol.0800621.Peer-Reviewed Original ResearchConceptsInfection of miceIFN responseT. cruzi-infected miceIFN-gamma-deficient miceIFN-gamma-producing cellsLevels of IFNEarly type IType I IFN receptorInnate immune responseIntradermal infection modelEarly host responseSite of infectionType I IFNT. cruziI IFN receptorLocal infection siteSite of inoculationType IIntradermal infectionImmune responseI IFNPrimary siteHost responseIFN receptorInfectionErythrocyte 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