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 Research
2022
Babesia 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 ResearchMeSH KeywordsAnimalsAtovaquoneBabesiaHumansMiceMice, Inbred C3HParasitesProdrugsQuinolonesTicksVirulenceConceptsLethal 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 relationshipsParasitemia
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
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