Featured Publications
Babesia BdFE1 esterase is required for the anti-parasitic activity of the ACE inhibitor fosinopril
Vydyam P, Choi J, Gihaz S, Chand M, Gewirtz M, Thekkiniath J, Lonardi S, Gennaro J, Mamoun C. Babesia BdFE1 esterase is required for the anti-parasitic activity of the ACE inhibitor fosinopril. Journal Of Biological Chemistry 2023, 299: 105313. PMID: 37797695, PMCID: PMC10663679, DOI: 10.1016/j.jbc.2023.105313.Peer-Reviewed Original ResearchConceptsAngiotensin converting enzyme (ACE) inhibitorsACE inhibitor fosinoprilTick-borne illnessConverting Enzyme InhibitorsVector-borne parasitic diseaseClass of drugsNovel drug targetsApicomplexan parasitesMass spectrometry analysisAnti-parasitic activityHeart failureSafe therapyParasite developmentDrug targetsEnzyme inhibitorsParasitic diseasesDrug resistanceTreatment of diseasesHuman babesiosisBabesia parasitesIntraerythrocytic parasitesSuch diseasesDiseaseSpectrometry analysisParasitesProperties and predicted functions of large genes and proteins of apicomplexan parasites
Fang T, Mohseni A, Lonardi S, Mamoun C. Properties and predicted functions of large genes and proteins of apicomplexan parasites. NAR Genomics And Bioinformatics 2024, 6: lqae032. PMID: 38584870, PMCID: PMC10993292, DOI: 10.1093/nargab/lqae032.Peer-Reviewed Original ResearchApicomplexan parasitesCausative agent of toxoplasmosisProtein sizeAgent of toxoplasmosisPathogen-host interactionsToxoplasma gondii</i>Conventional metabolic pathwaysCompact genomeEukaryotic organismsEncode proteinsEvolutionary constraintsNutrient acquisitionApicomplexan pathogensEvolutionary pressureAntigenic variationMetabolic pathwaysExpression patternsLarger proteinsParasitesCausative agentProteinGenesImmune evasionErythrocyte invasionPlasmodium falciparum</i>
2024
Insights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses
Singh P, Vydyam P, Fang T, Estrada K, Gonzalez L, Grande R, Kumar M, Chakravarty S, Berry V, Ranwez V, Carcy B, Depoix D, Sánchez S, Cornillot E, Abel S, Ciampossin L, Lenz T, Harb O, Sanchez-Flores A, Montero E, Le Roch K, Lonardi S, Mamoun C. Insights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses. Emerging Microbes & Infections 2024, 13: 2386136. PMID: 39148308, PMCID: PMC11370697, DOI: 10.1080/22221751.2024.2386136.Peer-Reviewed Original ResearchLeveraging genomic informationHuman babesiosisTick-borne diseasesDiseases of significanceCases of human babesiosisGenomic divergenceGenome sequenceGenomic informationMultigene familyGene functionBabesia divergensMammalian hostsAnimal healthMultiomics analysisZoonotic pathogensBabesiosisProtozoan parasitesVirulent strainsPathogensVertebrate hostsEnvironmental changesVirulenceReplication rateAntiparasitic drugsParasites
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
2021
Treatment of Human Babesiosis: Then and Now
Renard I, Ben Mamoun C. Treatment of Human Babesiosis: Then and Now. Pathogens 2021, 10: 1120. PMID: 34578153, PMCID: PMC8469882, DOI: 10.3390/pathogens10091120.Peer-Reviewed Original ResearchHuman babesiosisSevere adverse eventsNew therapeutic strategiesPublic health concernTick-borne diseaseAdverse eventsBlood transfusionCombination therapySafe therapyRisk of humanTherapeutic strategiesHuman transmissionApicomplexan parasitesDrug resistanceHealth concernBabesiosisTherapyTreatmentDiseaseCurrent arsenalParasitesRapid emergenceTransfusionClindamycinAzithromycinCytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Chiu JE, Renard I, George S, Pal A, Alday PH, Narasimhan S, Riscoe MK, Doggett JS, Mamoun C. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle. The Journal Of Infectious Diseases 2021, 225: 135-145. PMID: 34139755, PMCID: PMC8730496, DOI: 10.1093/infdis/jiab321.Peer-Reviewed Original ResearchConceptsMitochondrial cytochrome bParasite life cycleWild-type alleleTick vectorParasite fitnessCytochrome bMutant parasitesMutant allelesErythrocytic cycleArthropod vectorsNymphal stagesBabesia parasitesMutationsLife cycleFitnessTick stagesResistance mutationsMalaria-like illnessB. microtiAllelesDrug resistance mutationsParasitesHuman babesiosisTicksHost
2020
Anti-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
Evidence for vesicle-mediated antigen export by the human pathogen Babesia microti
Thekkiniath J, Kilian N, Lawres L, Gewirtz MA, Graham MM, Liu X, Ledizet M, Mamoun C. Evidence for vesicle-mediated antigen export by the human pathogen Babesia microti. Life Science Alliance 2019, 2: e201900382. PMID: 31196872, PMCID: PMC6572159, DOI: 10.26508/lsa.201900382.Peer-Reviewed Original ResearchConceptsApicomplexan parasitesCell fractionation studiesImmunoelectron microscopy analysisMode of secretionInvasion of erythrocytesParasite effectorsTrafficking motifsPlasma membraneExport mechanismClose relativesParasitophorous vacuoleHost erythrocyteMorphogenic changesFractionation studiesNovel mechanismHuman malariaFatal tick-borne diseaseMalaria-like illnessMouse red blood cellsParasitesAntigen exportTick-borne diseaseRed blood cellsHuman babesiosisImmunodominant antigens
2018
Establishment of a continuous in vitro culture of Babesia duncani in human erythrocytes reveals unusually high tolerance to recommended therapies
Abraham A, Brasov I, Thekkiniath J, Kilian N, Lawres L, Gao R, DeBus K, He L, Yu X, Zhu G, Graham MM, Liu X, Molestina R, Ben Mamoun C. Establishment of a continuous in vitro culture of Babesia duncani in human erythrocytes reveals unusually high tolerance to recommended therapies. Journal Of Biological Chemistry 2018, 293: 19974-19981. PMID: 30463941, PMCID: PMC6311517, DOI: 10.1074/jbc.ac118.005771.Peer-Reviewed Original ResearchConceptsHuman babesiosisBetter therapeutic strategiesHigher parasite burdenTick-borne diseaseFulminant infectionRed blood cellsTherapeutic strategiesHuman erythrocytesParasite burdenClinical casesSevere pathologyHuman red blood cellsNew disease modelsBlood cellsDisease modelsInfectionDiseaseBabesiosisDeathRelevant model systemParasitesApicomplexan parasitesDaughter parasitesErythrocytesFurther research
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 ResearchConceptsSDPM 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 ResearchConceptsPlasmodium 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