Featured Publications
The human malaria parasite Plasmodium falciparum can sense environmental changes and respond by antigenic switching
Schneider V, Visone J, Harris C, Florini F, Hadjimichael E, Zhang X, Gross M, Rhee K, Mamoun C, Kafsack B, Deitsch K. The human malaria parasite Plasmodium falciparum can sense environmental changes and respond by antigenic switching. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2302152120. PMID: 37068249, PMCID: PMC10151525, DOI: 10.1073/pnas.2302152120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigenic VariationGene Expression RegulationHumansMalaria, FalciparumParasitesPlasmodium falciparumProtozoan ProteinsConceptsGene switchingGene expressionHistone methyltransferasesHuman malaria parasite Plasmodium falciparumMalaria parasite Plasmodium falciparumS-adenosylmethionineGene expression patternsMulticopy gene familiesVariant surface proteinsParasite Plasmodium falciparumHuman malaria parasiteIntracellular S-adenosylmethioninePrincipal methyl donorEpigenetic controlGene familyActive genesAntigenic switchingGene transcriptionNutrient availabilityExpression patternsMethylation modificationSAM metabolismGenetic modificationAntigenic variationSurface proteins
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 pipelineApicoplastKalihinolTraffickingMalaria
2023
FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species
Sauer L, Canovas R, Roche D, Shams-Eldin H, Ravel P, Colinge J, Schwarz R, Ben Mamoun C, Rivals E, Cornillot E. FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species. Malaria Journal 2023, 22: 27. PMID: 36698187, PMCID: PMC9876418, DOI: 10.1186/s12936-022-04430-0.Peer-Reviewed Original ResearchConceptsGPI-APsOrder HaemosporidaGPI-APSequence diversityNew protein candidatesHost cell invasionHost-pathogen interactionsPlasmodium speciesGene duplicationHydrophobic helicesGPI anchorPlasma membraneDeletion eventsProtein candidatesProteomeCell invasionHaemosporidaProteinMalaria parasitesKey functionsDiverse groupSal-1ParasitesMalaria vaccine candidateSpecies
2020
Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling
Kilian N, Zhang Y, LaMonica L, Hooker G, Toomre D, Mamoun CB, Ernst AM. Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling. BioEssays 2020, 42: e1900145. PMID: 32342554, DOI: 10.1002/bies.201900145.Peer-Reviewed Original ResearchMeSH KeywordsClick ChemistryErythrocytesHumansMalaria, FalciparumMicroscopy, ElectronPlasmodium falciparumConceptsMetabolic labelingHuman malaria parasite Plasmodium falciparumProtein S-palmitoylationImportant post-translational modificationMalaria parasite Plasmodium falciparumComplex cell biologyPost-translational modificationsParasite Plasmodium falciparumTime-consuming generationAsexual developmental stagesPalmitoylated proteinsS-palmitoylationCell biologyP. falciparumTransgenic parasitesExtent of labelingDevelopmental stagesMicroscopy approachSingle-molecule switchingPlasmodium falciparum-infected erythrocytesFalciparum-infected erythrocytesPlasmodium falciparumFalciparumLabelingMicroscopic examinationAnti-PfGARP activates programmed cell death of parasites and reduces severe malaria
Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnädig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature 2020, 582: 104-108. PMID: 32427965, PMCID: PMC7372601, DOI: 10.1038/s41586-020-2220-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsAntibodies, ProtozoanAntigens, ProtozoanAotidaeApoptosisCaspasesChildCohort StudiesDNA, ProtozoanEnzyme ActivationErythrocytesFemaleHumansIntercellular Signaling Peptides and ProteinsKenyaMalaria VaccinesMalaria, FalciparumMaleMiceParasitesPlasmodium falciparumProtozoan ProteinsTanzaniaTrophozoitesVacuolesConceptsTrophozoite-infected erythrocytesSevere malariaParasite antigensLongitudinal cohort studyPlasma of childrenCell deathNon-human primatesCohort studyEffective vaccineTanzanian childrenParasite densityInvasion of hepatocytesStage parasitesMalariaPlasmodium falciparumAntibodiesFalciparumKenyan adolescentsVaccineAntigenErythrocytesDeathChildrenInvasionParasites
2019
Comparative 3D genome organization in apicomplexan parasites
Bunnik EM, Venkat A, Shao J, McGovern KE, Batugedara G, Worth D, Prudhomme J, Lapp SA, Andolina C, Ross LS, Lawres L, Brady D, Sinnis P, Nosten F, Fidock DA, Wilson EH, Tewari R, Galinski MR, Ben Mamoun C, Ay F, Le Roch KG. Comparative 3D genome organization in apicomplexan parasites. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 3183-3192. PMID: 30723152, PMCID: PMC6386730, DOI: 10.1073/pnas.1810815116.Peer-Reviewed Original ResearchConceptsGenome organizationGene expressionApicomplexan parasitesVirulence genesSpatial genome organizationPositioning of chromosomesRelated apicomplexan parasitesVirulence gene clusterClustering of centromeresHi-C experimentsStrong repressive effectHuman malaria parasiteChromosome foldingEukaryotic cellsGene familyGene clusterGenome modelGenomeGene clusteringMore virulent pathogensNuclear spaceRepressive effectGenesAntigenic variationVirulent pathogens
2015
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening
Choi JY, Kumar V, Pachikara N, Garg A, Lawres L, Toh J, Voelker DR, Ben Mamoun C. Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. Molecular Microbiology 2015, 99: 999-1014. PMID: 26585333, PMCID: PMC4898484, DOI: 10.1111/mmi.13280.Peer-Reviewed Original ResearchConceptsClass of enzymesDevelopment of antimicrobialsYeast genesMembrane biogenesisEukaryotic pathogensProenzyme processingMammalian cellsPhosphatidylserine decarboxylasePSD activityPhospholipid biosynthesisParasite enzymeEssential functionsGenetic studiesMetabolic analysisAmino acidsDecarboxylase enzymePhosphatidylethanolamine synthesisPosition 40Inhibitor screeningEssential roleYeastEnzymePlasmodium falciparumSuitable targetNovel class
2013
Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission
Bobenchik AM, Witola WH, Augagneur Y, Lochlainn L, Garg A, Pachikara N, Choi JY, Zhao YO, Usmani-Brown S, Lee A, Adjalley SH, Samanta S, Fidock DA, Voelker DR, Fikrig E, Mamoun C. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 18262-18267. PMID: 24145416, PMCID: PMC3831454, DOI: 10.1073/pnas.1313965110.Peer-Reviewed Original ResearchConceptsAsexual replicationGametocyte developmentFunctional complementation assaysPhosphoethanolamine N-methyltransferaseHost serineComplementation assaysMalaria transmissionGenetic diversityPhosphoethanolamine methyltransferaseGametocyte differentiationFemale gametocytesSpecificity of inhibitionMetabolic analysisSynthesis of phosphatidylcholineGametocytogenesisChemical screeningPlasmodium speciesAnopheles mosquitoesN-methyltransferaseLow micromolar rangePathwayReplicationHuman erythrocytesParasitesGlobal burden
2008
Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects*
Witola WH, El Bissati K, Pessi G, Xie C, Roepe PD, Mamoun CB. Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects*. Journal Of Biological Chemistry 2008, 283: 27636-27643. PMID: 18694927, PMCID: PMC2562060, DOI: 10.1074/jbc.m804360200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEthanolamineGene DeletionMethylationMethyltransferasesPhosphatidylcholinesPlasmodium falciparumProtozoan ProteinsSerineConceptsSDPM pathwayBiosynthesis of phosphatidylcholinePhosphatidylcholine biosynthesisParasite growthMajor membrane phospholipidsHuman malaria parasiteHost serineSerine decarboxylaseGenetic evidenceMethyltransferase enzymeSurvival defectGene resultsYeast cellsMethylation of phosphatidylethanolamineBiosynthesisSynthesis of phosphatidylcholineBiochemical studiesMembrane phospholipidsMalaria parasitesPlasmodium parasitesSevere growthPathwaySignificant defectsParasitesComplete lossGenetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum
Bissati K, Downie MJ, Kim SK, Horowitz M, Carter N, Ullman B, Mamoun C. Genetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum. Molecular And Biochemical Parasitology 2008, 161: 130-139. PMID: 18639591, PMCID: PMC2612043, DOI: 10.1016/j.molbiopara.2008.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsBiological TransportErythrocytesGene DeletionGuanineGuanosineMembrane Transport ProteinsPlasmodium falciparumProtozoan ProteinsPurinesXanthineConceptsPlasmodium falciparumPurine sourcePurine ring de novoP. falciparum parasitesP. falciparum strainsNon-physiological concentrationsFalciparum parasitesFalciparum strainsMalaria parasitesEpisomal complementationKnockout parasitesParasite strainsGenetic evidencePhysiological concentrationsPurine salvagePfNT1Functional rolePurine uptakeFalciparumAdenosineEssential roleParasitesDe novoGuanineXanthine
2006
The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum
Bissati K, Zufferey R, Witola WH, Carter NS, Ullman B, Mamoun C. The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9286-9291. PMID: 16751273, PMCID: PMC1482602, DOI: 10.1073/pnas.0602590103.Peer-Reviewed Original ResearchConceptsParasite plasma membraneHuman malaria parasite Plasmodium falciparumMalaria parasite Plasmodium falciparumParasite Plasmodium falciparumPurine salvagePlasma membraneLethal mutantsPlasmodium falciparumInosine transportPurine sourceSpecialized transportersTransgenic parasitesHost enzymesPfNT1Essential nutrientsPotential therapeutic targetParasitesPhysiological conditionsHost purinesInfected erythrocytesSequential pathwaySevere reductionTherapeutic targetP. falciparumHuman erythrocytes
2004
A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation
Pessi G, Kociubinski G, Mamoun CB. A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 6206-6211. PMID: 15073329, PMCID: PMC395947, DOI: 10.1073/pnas.0307742101.Peer-Reviewed Original Research
1999
A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum
Mamoun C, Gluzman I, Goyard S, Beverley S, Goldberg D. A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8716-8720. PMID: 10411941, PMCID: PMC17582, DOI: 10.1073/pnas.96.15.8716.Peer-Reviewed Original ResearchConceptsSelectable markerPlasmodium gene functionHuman malaria parasite Plasmodium falciparumMalaria parasite Plasmodium falciparumP. falciparum genomeBlasticidin S deaminaseParasite Plasmodium falciparumOnly selectable markerHuman malaria pathogenPlasmid copy numberEssential genesFalciparum genomeGene functionIndependent selectable markersPlasmodium falciparumGenomic informationGenetic manipulationGene promoterNeo expressionFunctional analysisPlasmid replicationTn 5Copy numberDihydrofolate reductaseMalaria pathogen