Featured Publications
Babesia 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 inhibitorProperties 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>
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 emergenceTransfusionClindamycinAzithromycinEffective 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
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 antigensComparative 3D genome organization in apicomplexan parasites
Bunnik EM, Venkat A, Shao J, McGovern KE, Batugedara G, Worth D, Prudhomme J, Lapp SA, Andolina C, Ross LS, Lawres L, Brady D, Sinnis P, Nosten F, Fidock DA, Wilson EH, Tewari R, Galinski MR, Ben Mamoun C, Ay F, Le Roch KG. Comparative 3D genome organization in apicomplexan parasites. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 3183-3192. PMID: 30723152, PMCID: PMC6386730, DOI: 10.1073/pnas.1810815116.Peer-Reviewed Original ResearchConceptsGenome organizationGene expressionApicomplexan parasitesVirulence genesSpatial genome organizationPositioning of chromosomesRelated apicomplexan parasitesVirulence gene clusterClustering of centromeresHi-C experimentsStrong repressive effectHuman malaria parasiteChromosome foldingEukaryotic cellsGene familyGene clusterGenome modelGenomeGene clusteringMore virulent pathogensNuclear spaceRepressive effectGenesAntigenic variationVirulent pathogens
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
2012
Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti†
Cornillot E, Hadj-Kaddour K, Dassouli A, Noel B, Ranwez V, Vacherie B, Augagneur Y, Brès V, Duclos A, Randazzo S, Carcy B, Debierre-Grockiego F, Delbecq S, Moubri-Ménage K, Shams-Eldin H, Usmani-Brown S, Bringaud F, Wincker P, Vivarès CP, Schwarz RT, Schetters TP, Krause PJ, Gorenflot A, Berry V, Barbe V, Mamoun C. Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti†. Nucleic Acids Research 2012, 40: 9102-9114. PMID: 22833609, PMCID: PMC3467087, DOI: 10.1093/nar/gks700.Peer-Reviewed Original ResearchConceptsGenome-wide phylogenetic analysisLateral transfer eventsSmallest nuclear genomesGenome-scale reconstructionB. microtiMinimal metabolic requirementsApicomplexan genomesMitochondrial genomeNuclear genomeProtozoan parasitismMultigene familyApicomplexan parasitesPhylum ApicomplexaPhylogenetic analysisNew cladeGenomeGenomic sequencingCopy numberTransfer eventsApicomplexaMetabolic requirementsBabesia microtiSequencingSpeciesProtozoa