2021
Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection
Oliva Chávez AS, Wang X, Marnin L, Archer NK, Hammond HL, Carroll EEM, Shaw DK, Tully BG, Buskirk AD, Ford SL, Butler LR, Shahi P, Morozova K, Clement CC, Lawres L, Neal A, Mamoun CB, Mason KL, Hobbs BE, Scoles GA, Barry EM, Sonenshine DE, Pal U, Valenzuela JG, Sztein MB, Pasetti MF, Levin ML, Kotsyfakis M, Jay SM, Huntley JF, Miller LS, Santambrogio L, Pedra JHF. Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection. Nature Communications 2021, 12: 3696. PMID: 34140472, PMCID: PMC8211691, DOI: 10.1038/s41467-021-23900-8.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumAnimalsArthropodsBacterial InfectionsCell LineDermacentorExtracellular VesiclesFrancisella tularensisGene OntologyHumansInflammationIntravital MicroscopyIxodesMaleMiceMice, Inbred C57BLMice, KnockoutMicroscopy, Electron, TransmissionProteomicsR-SNARE ProteinsSkinTandem Mass SpectrometryTicksT-LymphocytesVesicle-Associated Membrane Protein 2ConceptsExtracellular vesiclesBiology of arthropodsSynaptobrevin 2Pathogen Francisella tularensisMammalian hostsArthropodsVector feedingDistinct outcomesPathogen transmissionVesiclesMicrobial spreadingVector-borne diseasesFrancisella tularensisBacterial infectionsTicks DermacentorIxodes scapularisAnaplasma phagocytophilumBiologySkin immunitySnareDendritic epidermal T cellsPathogensHostT cellsTularensis
2020
Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma
Chung KM, Singh J, Lawres L, Dorans KJ, Garcia C, Burkhardt DB, Robbins R, Bhutkar A, Cardone R, Zhao X, Babic A, Vayrynen SA, Dias Costa A, Nowak JA, Chang DT, Dunne RF, Hezel AF, Koong AC, Wilhelm JJ, Bellin MD, Nylander V, Gloyn AL, McCarthy MI, Kibbey RG, Krishnaswamy S, Wolpin BM, Jacks T, Fuchs CS, Muzumdar MD. Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma. Cell 2020, 181: 832-847.e18. PMID: 32304665, PMCID: PMC7266008, DOI: 10.1016/j.cell.2020.03.062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell LineCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDisease ProgressionEndocrine CellsExocrine GlandsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLMutationObesityPancreatic NeoplasmsSignal TransductionTumor MicroenvironmentConceptsPancreatic ductal adenocarcinomaPDAC progressionDuctal adenocarcinomaMajor modifiable risk factorModifiable risk factorsBeta cell expressionObesity-associated changesAutochthonous mouse modelPancreatic ductal tumorigenesisDriver gene mutationsPeptide hormone cholecystokininRisk factorsPDAC developmentMouse modelObesityHormone cholecystokininOncogenic KrasCell expressionTumor microenvironmentDietary inductionCancer developmentGene mutationsReversible roleMurine samplesProgression
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
BmGPAC, 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 assayInsights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes
Virji AZ, Thekkiniath J, Ma W, Lawres L, Knight J, Swei A, Roch KL, Mamoun C. Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes. International Journal For Parasitology 2018, 49: 105-113. PMID: 30176236, PMCID: PMC6395566, DOI: 10.1016/j.ijpara.2018.05.008.Peer-Reviewed Original ResearchConceptsMitochondrial genomeApicoplast genomeB. duncaniCytochrome c oxidaseB. microtiOrganelle proteinsCircular moleculeApicomplexan parasitesPhylogenetic analysisNew lineageGene transcriptionCytochrome bGenomeC oxidaseI proteinPlasmodium sppProteinTheileria sppBabesia bovisKbParasite factorsCausative agentParasitesAnnotationSpp
2017
The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation
Chiu JE, Thekkiniath J, Choi JY, Perrin BA, Lawres L, Plummer M, Virji AZ, Abraham A, Toh JY, Zandt MV, Aly ASI, Voelker DR, Mamoun CB. The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation. Scientific Reports 2017, 7: 14234. PMID: 29079738, PMCID: PMC5660193, DOI: 10.1038/s41598-017-14074-9.Peer-Reviewed Original ResearchConceptsMode of actionBlood stage developmentPantothenate kinase activityYeast mutantsMass spectrometry analysisBlood-stage parasitesPA-dependent mannerKinase activityPantothenate phosphorylationCAB1Pantothenate kinaseStage parasitesYeast growthCoenzyme ABiochemical analysisBlood stagesDirect competitionPantothenic acidSpectrometry analysisResistant P. falciparum strainsPhosphorylationStage developmentPlasmodium falciparumCompetitive inhibitorP. berghei
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
2015
Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening
Choi JY, Kumar V, Pachikara N, Garg A, Lawres L, Toh J, Voelker DR, Ben Mamoun C. Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. Molecular Microbiology 2015, 99: 999-1014. PMID: 26585333, PMCID: PMC4898484, DOI: 10.1111/mmi.13280.Peer-Reviewed Original ResearchConceptsClass of enzymesDevelopment of antimicrobialsYeast genesMembrane biogenesisEukaryotic pathogensProenzyme processingMammalian cellsPhosphatidylserine decarboxylasePSD activityPhospholipid biosynthesisParasite enzymeEssential functionsGenetic studiesMetabolic analysisAmino acidsDecarboxylase enzymePhosphatidylethanolamine synthesisPosition 40Inhibitor screeningEssential roleYeastEnzymePlasmodium falciparumSuitable targetNovel class
2014
Plasmodium yoelii Vitamin B5 Pantothenate Transporter Candidate is Essential for Parasite Transmission to the Mosquito
Hart RJ, Lawres L, Fritzen E, Mamoun C, Aly AS. Plasmodium yoelii Vitamin B5 Pantothenate Transporter Candidate is Essential for Parasite Transmission to the Mosquito. Scientific Reports 2014, 4: 5665. PMID: 25012929, PMCID: PMC4092334, DOI: 10.1038/srep05665.Peer-Reviewed Original ResearchConceptsSexual blood stage developmentYeast cellsLife cycle stagesNon-photosynthetic cellsParasite plasma membraneMultiple parasite life cycle stagesParasite life cycle stagesBlood stage developmentPantothenate transportGene-targeting techniquesHuman malaria parasiteCycle stagesFunctional complementationPAT inhibitorsPlasma membraneSporozoite formationTransporter candidatesVivo functionOocyst stageP. falciparuminParasite transmissionPantothenate concentrationPantothenate uptakeCoenzyme AMalaria parasites