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 propertiesMonotherapyTafenoquine-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 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
Specific 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 babesiosis
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
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