Featured Publications
An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Hart T, Sonnert N, Tang X, Chaurasia R, Allen P, Hunt J, Read C, Johnson E, Arora G, Dai Y, Cui Y, Chuang Y, Yu Q, Rahman M, Mendes M, Rolandelli A, Singh P, Tripathi A, Ben Mamoun C, Caimano M, Radolf J, Lin Y, Fingerle V, Margos G, Pal U, Johnson R, Pedra J, Azad A, Salje J, Dimopoulos G, Vinetz J, Carlyon J, Palm N, Fikrig E, Ring A. An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms. Cell 2024, 187: 4113-4127.e13. PMID: 38876107, DOI: 10.1016/j.cell.2024.05.023.Peer-Reviewed Original ResearchCell invasionHost-microbe interactionsArthropod-borne pathogensHost sensingMicrobe interactionsTranscriptional regulationLyme disease spirocheteMicrobial interactionsExtracellular proteinsMicrobial pathogenesisEpidermal growth factorTissue colonizationEnvironmental cuesBacterial selectivityIntracellular pathogensPutative interactionsNext-generation therapeuticsPathogensFunctional investigationsInteractomeVector-borne diseasesImmune evasionPathogenic mechanismsStrainUnmet medical needEffectiveness of Two New Endochin-like Quinolones, ELQ-596 and ELQ-650, in Experimental Mouse Models of Human Babesiosis
Vydyam P, Chand M, Pou S, Winter R, Liebman K, Nilsen A, Doggett J, Riscoe M, Mamoun C. Effectiveness of Two New Endochin-like Quinolones, ELQ-596 and ELQ-650, in Experimental Mouse Models of Human Babesiosis. ACS Infectious Diseases 2024, 10: 1405-1413. PMID: 38563132, PMCID: PMC11127568, DOI: 10.1021/acsinfecdis.4c00143.Peer-Reviewed Original ResearchConceptsRadical cureEndochin-like quinolonesAgent of human malariaLethal infection modelTreatment of human babesiosisLow toxicity profileExperimental mouse modelImmunocompetent miceImmunocompromised miceFavorable pharmacological propertiesHuman malariaToxicity profileChronic modelHuman babesiosisAnimal modelsInfection modelPharmacological limitationsActivity in vitroPharmacological propertiesReduce infectionQuinolonesMiceMitochondrial electron transport chainFavorable physicochemical propertiesMonotherapyBabesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies
Fang T, Mamoun C. Babesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies. The Journal Of Infectious Diseases 2024, 230: 263-270. PMID: 39052743, PMCID: PMC11272067, DOI: 10.1093/infdis/jiae191.Peer-Reviewed Original ResearchConsequences of malariaDevelopment of future therapiesIntraerythrocytic parasitesHost red blood cellsDrugs in vitroB. duncaniIn vitro culture systemRed blood cellsFuture therapiesTherapeutic strategiesAnimal modelsWell-annotated genomeBlood cellsResistance mechanismsPathological consequencesMode of actionBabesia duncaniCulture systemParasite biologyPathogensMalariaPlasmodiumTherapyAnimalsCulture conditionsTafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis
Vydyam P, Pal A, Renard I, Chand M, Kumari V, Gennaro J, Mamoun C. Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis. The Journal Of Infectious Diseases 2024, 229: 161-172. PMID: 38169301, PMCID: PMC10786256, DOI: 10.1093/infdis/jiad315.Peer-Reviewed Original ResearchBabesia 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 analysisParasitesThe 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 ResearchConceptsGene 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 proteinsBabesia 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 inhibitorResponse to the Letter by Liu and Colleagues
Mamoun C, Vydyam P. Response to the Letter by Liu and Colleagues. The Journal Of Infectious Diseases 2024, 229: 1601-1601. PMID: 38471083, DOI: 10.1093/infdis/jiae084.Peer-Reviewed Original ResearchReply to Dow and Smith
Mamoun C, Wormser G. Reply to Dow and Smith. The Journal Of Infectious Diseases 2024, 230: 273-273. PMID: 39052753, DOI: 10.1093/infdis/jiae194.Peer-Reviewed Original ResearchProperties 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
A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents
Barnes G, Magann N, Perrotta D, Hörmann F, Fernandez S, Vydyam P, Choi J, Prudhomme J, Neal A, Le Roch K, Mamoun C, Vanderwal C. A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents. Journal Of The American Chemical Society 2024, 146: 29883-29894. PMID: 39412402, PMCID: PMC11528414, DOI: 10.1021/jacs.4c11897.Peer-Reviewed Original ResearchNatural productsLarock indole synthesisAlkaloid natural productsAmine nucleophilesDivergent synthesisIndole synthesisPyrrolic nitrogenMethoxy groupLead compoundsDrug discoveryCompoundsStructural analogsPlasmodium falciparum</i>SynthesisPyrroloiminoquinoneHuman cytotoxicityMalaria parasitesNucleophilesPyrroleAntiprotozoal agentsAminesMammalian cellsIntermediateA fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis
Singh P, Choi J, Wang W, Lam T, Lechner P, Vanderwal C, Pou S, Nilsen A, Mamoun C. A fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis. Journal Of Biological Chemistry 2024, 300: 107832. PMID: 39342998, PMCID: PMC11541840, DOI: 10.1016/j.jbc.2024.107832.Peer-Reviewed Original ResearchAminopropyl transferaseFluorescence-based assayLack of high-throughput assaysHigh-throughput screeningCarbon chain lengthChemical librariesMass spectrometryChain lengthHigh-throughput assayDrug discoveryMass spectrometry analysisSaccharomyces cerevisiaeThin-layer chromatographyFluorescence intensityCellular functionsSpectrometry analysisPolycationic moleculesFluorescent conjugatesIsoindoleAPT activityCatalysisAssayBenzeneAdductsEnzymeA 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 pipelineApicoplastKalihinolTraffickingMalariaInsights 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 drugsParasitesIn vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites
Vydyam P, Chand M, Gihaz S, Renard I, Heffernan G, Jacobus L, Jacobus D, Saionz K, Shah R, Shieh H, Terpinski J, Zhao W, Cornillot E, Mamoun C. In vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites. Antimicrobial Agents And Chemotherapy 2024, 68: e00423-24. PMID: 39136469, PMCID: PMC11373198, DOI: 10.1128/aac.00423-24.Peer-Reviewed Original ResearchTherapeutic indexPlasmodium falciparum</i>Effective therapeutic strategyCausative agent of babesiosisIn vitro efficacyAntiparasitic drugsProtozoan parasitesMalaria parasitesIntraerythrocytic protozoan parasiteTherapeutic strategiesFolate pathwayBroad-spectrum antiparasitic drugStrain HB3Babesia divergensMalariaBabesia duncaniAnimal healthAntifolatesDrugWidespread resistanceCausative agentBiguanideBabesiaBabesiosisBiosynthesis of purinesA set of diagnostic tests for detection of active Babesia duncani infection
Chand M, Vydyam P, Pal A, Thekkiniath J, Darif D, Li Z, Choi J, Magni R, Luchini A, Tonnetti L, Horn E, Tufts D, Ben Mamoun C. A set of diagnostic tests for detection of active Babesia duncani infection. International Journal Of Infectious Diseases 2024, 147: 107178. PMID: 39025200, DOI: 10.1016/j.ijid.2024.107178.Peer-Reviewed Original ResearchB. microtiB. duncaniBlood samplesLife-threatening infectionsAntigen capture assayTick-borne diseasesFatal tick-borne diseaseP. falciparumBabesia genusScreening of blood samplesBabesia speciesB. divergensActive infectionAccurate diagnosisEffective disease managementPoint-of-care testingDiagnostic testsReservoir hostsBabesiaInfectionHuman babesiosisIntraerythrocytic parasitesImmunodominant antigensMolecular assaysCapture assayVitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi
Choi J, Gihaz S, Munshi M, Singh P, Vydyam P, Hamel P, Adams E, Sun X, Khalimonchuk O, Fuller K, Ben Mamoun C. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Communications Biology 2024, 7: 894. PMID: 39043829, PMCID: PMC11266677, DOI: 10.1038/s42003-024-06595-7.Peer-Reviewed Original ResearchConceptsSusceptibility of fungiRegulation of genesMetabolism of fatty acidsVacuolar morphologySaccharomyces cerevisiaeAcetyl-CoAEukaryotic pathogensGenetic evidenceGenetic regulationCellular processesAntifungal drugsCo-enzyme ADrug detoxificationAntifungal therapyDrug-resistant strainsFungal infectionsMitochondrial functionFungiAmino acidsAR-12Vitamin B5Synthase activityPathwayExcellent targetGlobal health threat
2023
Maturation of the malarial phosphatidylserine decarboxylase is mediated by high affinity binding to anionic phospholipids
Choi J, Lopes L, Mamoun C, Voelker D. Maturation of the malarial phosphatidylserine decarboxylase is mediated by high affinity binding to anionic phospholipids. Journal Of Biological Chemistry 2023, 299: 104659. PMID: 36997087, PMCID: PMC10172927, DOI: 10.1016/j.jbc.2023.104659.Peer-Reviewed Original ResearchConceptsPS decarboxylaseFT-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
2022
Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress
Ceccatelli Berti C, Gihaz S, Figuccia S, Choi J, Pal A, Goffrini P, Ben Mamoun C. Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress. International Journal Of Molecular Sciences 2022, 24: 435. PMID: 36613877, PMCID: PMC9820505, DOI: 10.3390/ijms24010435.Peer-Reviewed Original ResearchConceptsPantothenate Kinase-Associated NeurodegenerationFunctional conservationMitochondrial transit peptidePantothenate kinaseNormal cellular activitiesUse of yeastOverexpression of humanTransit peptideConserved functionYeast mutantsModel organismsPanK activityCellular functionsOxidative stressCellular conditionsMitochondrial homeostasisCellular cofactorsDefective growthKinase isoformsCellular activitiesMetabolic pathwaysYeastGenesMitochondrial dysfunctionBiochemical properties