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
Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions
Silva JC, Cornillot E, McCracken C, Usmani-Brown S, Dwivedi A, Ifeonu OO, Crabtree J, Gotia HT, Virji AZ, Reynes C, Colinge J, Kumar V, Lawres L, Pazzi JE, Pablo JV, Hung C, Brancato J, Kumari P, Orvis J, Tretina K, Chibucos M, Ott S, Sadzewicz L, Sengamalay N, Shetty AC, Su Q, Tallon L, Fraser CM, Frutos R, Molina DM, Krause PJ, Ben Mamoun C. Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions. Scientific Reports 2016, 6: 35284. PMID: 27752055, PMCID: PMC5082761, DOI: 10.1038/srep35284.Peer-Reviewed Original ResearchConceptsGene expression profilingExpression profilingGenome-wide diversityHost-parasite interactionsHost-pathogen interactionsParasite secretomeParasite evolutionIntraerythrocytic protozoan parasiteGenome compositionGenetic diversityImmuno-proteomic approachSurface proteomeGenetic variationMammalian hostsSmall mammalsSelective pressurePolymorphic genesGenesFirst insightProtozoan parasiteBabesia microtiSecretomeProteome arrayStrong host immune responseHost immune responseRadical 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 activityAtovaquoneA targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti
Cornillot E, Dassouli A, Pachikara N, Lawres L, Renard I, Francois C, Randazzo S, Brès V, Garg A, Brancato J, Pazzi JE, Pablo J, Hung C, Teng A, Shandling AD, Huynh VT, Krause PJ, Lepore T, Delbecq S, Hermanson G, Liang X, Williams S, Molina DM, Ben Mamoun C. A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti. Transfusion 2016, 56: 2085-2099. PMID: 27184823, PMCID: PMC5644385, DOI: 10.1111/trf.13640.Peer-Reviewed Original ResearchConceptsB. microti antibodiesTransfusion-transmitted babesiosisMicroti antibodiesB. microti-infected miceImmunomics approachBabesia microtiB. microti infectionPromising candidate biomarkerBlood screeningMicroti infectionPast infectionBlood donorsHealth burdenBlood supplyImmune responseAntibody assaysAcute babesiosisEndemic areasHuman studiesBabesiosis infectionDrug AdministrationCandidate biomarkersGood biomarkerStudy designInfection