Featured Publications
Effectiveness 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 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 analysisParasites
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 drugsParasitesA 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 assay
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 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. microtiSpecific 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 babesiosisBabesia 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
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
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
2016
Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone
Lawres LA, Garg A, Kumar V, Bruzual I, Forquer IP, Renard I, Virji AZ, Boulard P, Rodriguez EX, Allen AJ, Pou S, Wegmann KW, Winter RW, Nilsen A, Mao J, Preston DA, Belperron AA, Bockenstedt LK, Hinrichs DJ, Riscoe MK, Doggett JS, Mamoun C. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone. Journal Of Experimental Medicine 2016, 213: 1307-1318. PMID: 27270894, PMCID: PMC4925016, DOI: 10.1084/jem.20151519.Peer-Reviewed Original ResearchConceptsExperimental babesiosisHuman babesiosisImmunodeficient miceRadical cureELQ-334Discontinuation of therapyFuture clinical evaluationEndochin-like quinolonesVivo efficacy studiesAdverse side effectsRecrudescent parasitesMost clinical casesCombination therapyMultisystem diseaseClinical evaluationComplete clearanceCurrent treatmentDrug combinationsDrug failureSide effectsExcellent growth inhibitory activityEfficacy studiesClinical casesGrowth inhibitory activityAtovaquone