Featured Publications
Babesia duncani multi-omics identifies virulence factors and drug targets
Singh P, Lonardi S, Liang Q, Vydyam P, Khabirova E, Fang T, Gihaz S, Thekkiniath J, Munshi M, Abel S, Ciampossin L, Batugedara G, Gupta M, Lu X, Lenz T, Chakravarty S, Cornillot E, Hu Y, Ma W, Gonzalez L, Sánchez S, Estrada K, Sánchez-Flores A, Montero E, Harb O, Le Roch K, Mamoun C. Babesia duncani multi-omics identifies virulence factors and drug targets. Nature Microbiology 2023, 8: 845-859. PMID: 37055610, PMCID: PMC10159843, DOI: 10.1038/s41564-023-01360-8.Peer-Reviewed Original ResearchConceptsDrug targetsVirulence factorsCandidate virulence factorsRNA-seq dataIntraerythrocytic life cycleAttractive drug targetB. duncaniNuclear genomeGenome annotationApicomplexan parasitesApicomplexan pathogensEpigenetic profilesEpigenetic analysisParasite metabolismMalaria-like diseaseHuman erythrocytesLife cycle stagesBabesia speciesGenomeMetabolic requirementsCycle stagesLife cycleBiologySmall moleculesPotent inhibitor
2021
Cytochrome 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
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
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 researchBmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti Infection
Thekkiniath J, Mootien S, Lawres L, Perrin BA, Gewirtz M, Krause PJ, Williams S, Doggett J, Ledizet M, Mamoun C. BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti Infection. Journal Of Clinical Microbiology 2018, 56: 10.1128/jcm.00067-18. PMID: 30093394, PMCID: PMC6156295, DOI: 10.1128/jcm.00067-18.Peer-Reviewed Original ResearchConceptsHuman babesiosisBabesia microti infectionCapture enzyme-linked immunosorbent assayAntigen capture enzyme-linked immunosorbent assayAntigen capture assayEnzyme-linked immunosorbent assayZoonotic infectious diseaseAcute infectionBlood transfusionAsymptomatic infectionMicroti infectionReal-time PCRBlood supplyAnimal reservoir hostsDonor bloodEpidemiological surveyHuman patientsImmune systemSerological assaysImmunodominant antigensInfectionInfectious diseasesIntraerythrocytic protozoan parasitePatientsImmunosorbent assay
2008
Genetic 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