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 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 Anti-Parasitic Therapeutic Strategies
Fang T, Mamoun C. Babesia duncani, A Model Organism for Investigating Intraerythrocytic Parasitism and Novel Anti-Parasitic Therapeutic Strategies. The Journal Of Infectious Diseases 2024, jiae191. PMID: 38626187, 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, jiae194. PMID: 38712965, 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>
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 propertiesEpitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
Chand M, Choi J, Pal A, Singh P, Kumari V, Thekkiniath J, Gagnon J, Timalsina S, Gaur G, Williams S, Ledizet M, Mamoun C. Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti. Frontiers In Cellular And Infection Microbiology 2022, 12: 1039197. PMID: 36506011, PMCID: PMC9732259, DOI: 10.3389/fcimb.2022.1039197.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesAntigen detection assaysMajor immunogenic determinantMost clinical casesReliable biomarkersAntibody combinationsImmunogenic determinantsIntraerythrocytic life cycleClinical casesUnique epitopesBabesia microtiEpitope profilingHuman babesiosisTick-borne diseasesSignificant riseSerological profilingPlasma samplesAntibodiesSerological characterizationProtozoan parasitePublic healthInfectionAntigenDiseaseMammalian hostsBabesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy.
Kumari V, Pal A, Singh P, Mamoun C. Babesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy. Bio-protocol 2022, 12 PMID: 36620533, PMCID: PMC9795036, DOI: 10.21769/bioprotoc.4549.Peer-Reviewed Original ResearchMouse modelHuman red blood cellsRed blood cellsC3H/HeJ miceBlood cellsHuman babesiosisMalaria-like illnessB. duncaniImportant health impactsTick-borne diseaseBlood transfusionTick biteLethal infectionHeJ miceRare caseBabesia duncaniImmunocompromised miceAnimal modelsHuman infectionsParasitic diseasesBabesia microtiDiseaseElderly peopleIntraerythrocytic parasitesB. microtiHigh-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development
Gihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development. Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.Peer-Reviewed Original ResearchConceptsCrystal structureHigh-throughput chemical screenHigh-resolution crystal structuresAntifungal drug developmentHigh-affinity inhibitorsEukaryotic pathogensChemical screenNew compoundsSingle chemotypeFunctional analysisLigand bindingAntifungal developmentPantothenate phosphorylationFungal isolatesPantothenate kinaseNew targetsFungiPanKPromising targetEnzymeDrug developmentNew mechanismCatalysisBiosynthesisKinaseSpecific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12
Gagnon J, Timalsina S, Choi JY, Chand M, Singh P, Lamba P, Gaur G, Pal AC, Mootien S, Marcos LA, Mamoun C, Ledizet M. Specific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12. Journal Of Clinical Microbiology 2022, 60: e00925-22. PMID: 36040206, PMCID: PMC9491189, DOI: 10.1128/jcm.00925-22.Peer-Reviewed Original ResearchConceptsB. microti infectionActive infectionMonoclonal antibodiesMicroti infectionTime of diagnosisMalaria-like illnessUrgent public health concernAntigen capture assayHost red blood cellsPublic health concernCapture assayEvaluation of clearanceElderly patientsRed blood cellsBlood transfusionDrug treatmentEarly diagnosisPosttreatment samplesBabesia microtiHealth concernInfected humansInfectionDiagnosisBlood cellsHuman babesiosisAn Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes
Singh P, Pal AC, Mamoun CB. An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes. Pathogens 2022, 11: 599. PMID: 35631120, PMCID: PMC9146245, DOI: 10.3390/pathogens11050599.Peer-Reviewed Original ResearchBabesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo
Pal AC, Renard I, Singh P, Vydyam P, Chiu JE, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo. The Journal Of Infectious Diseases 2022, 226: 1267-1275. PMID: 35512141, PMCID: PMC10233494, DOI: 10.1093/infdis/jiac181.Peer-Reviewed Original ResearchConceptsLethal infectionC3H/HeJ miceMalaria-like illnessB. duncaniMouse genetic backgroundSurvival outcomesHeJ miceSevere diseaseBabesia duncaniMouse modelDifferent mouse genetic backgroundsDrug susceptibilityBabesia microtiHuman babesiosisIntraerythrocytic parasitesUnique pathogenParasite loadMiceSpecies of BabesiaApicomplexa phylumInfectionBabesia parasitesFree merozoitesHuman erythrocytesGenetic backgroundRedesigning therapies for pantothenate kinase–associated neurodegeneration
Munshi MI, Yao SJ, Mamoun C. Redesigning therapies for pantothenate kinase–associated neurodegeneration. Journal Of Biological Chemistry 2022, 298: 101577. PMID: 35041826, PMCID: PMC8861153, DOI: 10.1016/j.jbc.2022.101577.Peer-Reviewed Original ResearchConceptsPantothenate kinase-associated neurodegenerationCellular metabolic processesMore common diseasesMetabolic processesPhysiological importancePANK2 genePantothenate kinaseCoenzyme ACoenzyme A.Rare genetic disorderCommon neurodegenerative diseaseNeurodegenerative diseasesGenetic disordersNeurodegenerationNew avenuesBiosynthesisKinaseGenesNew lightFuture investigationsCofactorMutationsCommon diseaseEnzymeAlzheimer's disease