Featured Publications
Babesia 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 inhibitorRole of a patatin-like phospholipase in Plasmodium falciparum gametogenesis and malaria transmission
Singh P, Alaganan A, More K, Lorthiois A, Thiberge S, Gorgette O, Guillotte Blisnick M, Guglielmini J, Aguilera S, Touqui L, Singh S, Chitnis C. Role of a patatin-like phospholipase in Plasmodium falciparum gametogenesis and malaria transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 17498-17508. PMID: 31413195, PMCID: PMC6717283, DOI: 10.1073/pnas.1900266116.Peer-Reviewed Original ResearchConceptsFemale gametesPerforin-like proteinBlood-stage growthIngestion of gametocytesProcess of gametogenesisPatatin-like phospholipaseGamete egressDiverse organismsMembrane remodelingIntracellular vesiclesVesicle secretionVesicular dischargeMale gametesOocyst formationPeripheral membraneGametocyte developmentGametogenesisExtensive membraneConditional deletionGametesBlood mealDevelopment of drugsDeletionPotential targetGenes
2024
A fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis
Singh P, Choi J, Wang W, T Lam T, Lechner P, Vanderwal C, Pou S, Nilsen A, Ben Mamoun C. A fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis. Journal Of Biological Chemistry 2024, 300: 107832. PMID: 39342998, DOI: 10.1016/j.jbc.2024.107832.Peer-Reviewed Original ResearchAminopropyl transferaseFluorescence-based assayLack of high-throughput assaysHigh-throughput screeningCarbon chain lengthChemical librariesMass spectrometryChain lengthHigh-throughput assayDrug discoveryMass spectrometry analysisSaccharomyces cerevisiaeThin-layer chromatographyFluorescence intensityCellular functionsSpectrometry analysisPolycationic moleculesFluorescent conjugatesIsoindoleAPT activityCatalysisAssayBenzeneAdductsEnzymeInsights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses
Singh P, Vydyam P, Fang T, Estrada K, Gonzalez L, Grande R, Kumar M, Chakravarty S, Berry V, Ranwez V, Carcy B, Depoix D, Sánchez S, Cornillot E, Abel S, Ciampossin L, Lenz T, Harb O, Sanchez-Flores A, Montero E, Le Roch K, Lonardi S, Mamoun C. Insights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses. Emerging Microbes & Infections 2024, 13: 2386136. PMID: 39148308, PMCID: PMC11370697, DOI: 10.1080/22221751.2024.2386136.Peer-Reviewed Original ResearchLeveraging genomic informationHuman babesiosisTick-borne diseasesDiseases of significanceCases of human babesiosisGenomic divergenceGenome sequenceGenomic informationMultigene familyGene functionBabesia divergensMammalian hostsAnimal healthMultiomics analysisZoonotic pathogensBabesiosisProtozoan parasitesVirulent strainsPathogensVertebrate hostsEnvironmental changesVirulenceReplication rateAntiparasitic drugsParasitesVitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi
Choi J, Gihaz S, Munshi M, Singh P, Vydyam P, Hamel P, Adams E, Sun X, Khalimonchuk O, Fuller K, Ben Mamoun C. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Communications Biology 2024, 7: 894. PMID: 39043829, PMCID: PMC11266677, DOI: 10.1038/s42003-024-06595-7.Peer-Reviewed Original ResearchConceptsSusceptibility of fungiRegulation of genesMetabolism of fatty acidsVacuolar morphologySaccharomyces cerevisiaeAcetyl-CoAEukaryotic pathogensGenetic evidenceGenetic regulationCellular processesAntifungal drugsCo-enzyme ADrug detoxificationAntifungal therapyDrug-resistant strainsFungal infectionsMitochondrial functionFungiAmino acidsAR-12Vitamin B5Synthase activityPathwayExcellent targetGlobal health threat
2022
Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
Chand M, Choi J, Pal A, Singh P, Kumari V, Thekkiniath J, Gagnon J, Timalsina S, Gaur G, Williams S, Ledizet M, Mamoun C. Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti. Frontiers In Cellular And Infection Microbiology 2022, 12: 1039197. PMID: 36506011, PMCID: PMC9732259, DOI: 10.3389/fcimb.2022.1039197.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesAntigen detection assaysMajor immunogenic determinantMost clinical casesReliable biomarkersAntibody combinationsImmunogenic determinantsIntraerythrocytic life cycleClinical casesUnique epitopesBabesia microtiEpitope profilingHuman babesiosisTick-borne diseasesSignificant riseSerological profilingPlasma samplesAntibodiesSerological characterizationProtozoan parasitePublic healthInfectionAntigenDiseaseMammalian hostsBabesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy.
Kumari V, Pal A, Singh P, Mamoun C. Babesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy. Bio-protocol 2022, 12 PMID: 36620533, PMCID: PMC9795036, DOI: 10.21769/bioprotoc.4549.Peer-Reviewed Original ResearchMouse modelHuman red blood cellsRed blood cellsC3H/HeJ miceBlood cellsHuman babesiosisMalaria-like illnessB. duncaniImportant health impactsTick-borne diseaseBlood transfusionTick biteLethal infectionHeJ miceRare caseBabesia duncaniImmunocompromised miceAnimal modelsHuman infectionsParasitic diseasesBabesia microtiDiseaseElderly peopleIntraerythrocytic parasitesB. microtiSpecific 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 babesiosisAn Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes
Singh P, Pal AC, Mamoun CB. An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes. Pathogens 2022, 11: 599. PMID: 35631120, PMCID: PMC9146245, DOI: 10.3390/pathogens11050599.Peer-Reviewed Original ResearchBabesia 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 ResearchConceptsLethal 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 relationshipsParasitemiaEvidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients
George S, Pal AC, Gagnon J, Timalsina S, Singh P, Vydyam P, Munshi M, Chiu JE, Renard I, Harden CA, Ott IM, Watkins AE, Vogels CBF, Lu P, Tokuyama M, Venkataraman A, Casanovas-Massana A, Wyllie AL, Rao V, Campbell M, Farhadian SF, Grubaugh ND, Dela Cruz CS, Ko AI, Perez A, Akaho EH, Moledina DG, Testani J, John AR, Ledizet M, Mamoun CB, Team A. Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients. Kidney360 2021, 2: 924-936. PMID: 35373072, PMCID: PMC8791366, DOI: 10.34067/kid.0002172021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 spike proteinSARS-CoV-2Spike proteinUrine samplesSARS-CoV-2 infectionYale-New Haven HospitalCOVID-19 patientsAntigen capture assayDetectable viral RNANew Haven HospitalPositive PCR resultsPossible long-term consequencesSpike S1 proteinNP PCRChildren's HospitalNasopharyngeal swabsSARS-CoV-2 spike S1 proteinRenal abnormalitiesLong-term effectsCystatin CLong-term consequencesHospitalUrineViral RNAAlbuminuria
2017
Molecular mechanisms that mediate invasion and egress of malaria parasites from red blood cells
Alaganan A, Singh P, Chitnis C. Molecular mechanisms that mediate invasion and egress of malaria parasites from red blood cells. Current Opinion In Hematology 2017, 24: 208-214. PMID: 28306665, DOI: 10.1097/moh.0000000000000334.Peer-Reviewed Original ResearchConceptsMalaria parasitesMolecular mechanismsPerforin-like proteinComplex life cycleHost cell invasionDiverse host cellsCurrent understandingDevelopment of inhibitorsDifferent life cycle stagesFemale gametesTimely secretionKey effector moleculesRegulated mannerMolecular basisFemale gametocytesVesicular organellesMosquito midgutFemale anopheline mosquitoesProtein ligandsHost cellsLife cycle stagesCell invasionFunctional roleEffector moleculesParasite growth
2016
Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes
Bargieri D, Thiberge S, Tay C, Carey A, Rantz A, Hischen F, Lorthiois A, Straschil U, Singh P, Singh S, Triglia T, Tsuboi T, Cowman A, Chitnis C, Alano P, Baum J, Pradel G, Lavazec C, Ménard R. Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes. Cell Host & Microbe 2016, 20: 618-630. PMID: 27832590, PMCID: PMC5104695, DOI: 10.1016/j.chom.2016.10.015.Peer-Reviewed Original ResearchConceptsFamily proteinsGamete egressParasite motilityCell invasionErythrocyte invasionMembrane disruptionParasitophorous vacuole membraneMalaria parasite PlasmodiumBlood stage formsApicomplexan parasitesVacuole membraneExtracellular environmentParasite PlasmodiumActomyosin motorParasite transmissionTRAP proteinProteinCell egressStage formsInvasionEgressFalciparum parasitesParasitesIntegral roleMotility