Featured Publications
Tafenoquine-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 analysisParasitesBabesia 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
2022
Epitope 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 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 background
2021
Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection
Chiu JE, Renard I, Pal AC, Singh P, Vydyam P, Thekkiniath J, Kumar M, Gihaz S, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection. Antimicrobial Agents And Chemotherapy 2021, 65: 10.1128/aac.00662-21. PMID: 34152821, PMCID: PMC8370247, DOI: 10.1128/aac.00662-21.Peer-Reviewed Original ResearchConceptsEndochin-like quinolonesLethal infectionBlood-borne diseasesBlood-borne pathogensEffective therapyRelated apicomplexan parasitesExperimental therapiesLow doseMouse modelInfectious agentsHuman infectionsInfectionClinical candidatesStrong efficacyB. microtiExcellent safetyMode of actionTherapyErythrocytic developmentAtovaquoneEfficacyApicomplexan parasitesSafetyStructure-activity relationshipsParasitemiaCytochrome 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
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