2024
Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection
Samaddar S, Rolandelli A, O’Neal A, Laukaitis-Yousey H, Marnin L, Singh N, Wang X, Butler L, Rangghran P, Kitsou C, Cabrera Paz F, Valencia L, R. Ferraz C, Munderloh U, Khoo B, Cull B, Rosche K, Shaw D, Oliver J, Narasimhan S, Fikrig E, Pal U, Fiskum G, Polster B, Pedra J. Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection. Nature Microbiology 2024, 9: 2278-2291. PMID: 38997520, DOI: 10.1038/s41564-024-01756-0.Peer-Reviewed Original ResearchMetabolic reprogrammingInfection of tick cellsInvestigate metabolic reprogrammingTick cellsLyme disease spirochete Borrelia burgdorferiSusceptibility to infectionArthropod-borne pathogensMetabolomics approachRickettsia buchneriHuman pathogensMetabolite allocationDiminished survivalBacterium Anaplasma phagocytophilumSpirochete Borrelia burgdorferiAcid metabolismA. phagocytophilum infectionInterspecies relationshipsElevated levelsInfectionFeeding impairmentHuman granulocytic anaplasmosisMetabolic responseArthropod vectorsI. scapularisPathogens
2023
Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector
Mazuecos L, Alberdi P, Hernández-Jarguín A, Contreras M, Villar M, Cabezas-Cruz A, Simo L, González-García A, Díaz-Sánchez S, Neelakanta G, Bonnet S, Fikrig E, de la Fuente J. Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector. IScience 2023, 26: 106697. PMID: 37168564, PMCID: PMC10165458, DOI: 10.1016/j.isci.2023.106697.Peer-Reviewed Original ResearchHuman granulocytic anaplasmosisPathogen infection/transmissionTick-borne pathogensTick-borne diseasesInfection/transmissionTick vectorGranulocytic anaplasmosisWildtype populationTick microbiotaPathogensModel pathogenTransovarialAnaplasmosisMSP4TicksAssociated reductionCompetitionLarvaeDisease riskParatransgenesisSymbiontsInfectionCommensal bacteriaBacteriaControl
2017
Pathogen-mediated manipulation of arthropod microbiota to promote infection
Abraham NM, Liu L, Jutras BL, Yadav AK, Narasimhan S, Gopalakrishnan V, Ansari JM, Jefferson KK, Cava F, Jacobs-Wagner C, Fikrig E. Pathogen-mediated manipulation of arthropod microbiota to promote infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e781-e790. PMID: 28096373, PMCID: PMC5293115, DOI: 10.1073/pnas.1613422114.Peer-Reviewed Original ResearchConceptsTerminal D-alanine residueHuman pathogensPathogen-mediated manipulationNumerous human pathogensCapacity of bacteriaWay microbesArthropod microbiotaD-alanine residuesA. phagocytophilumAntibacterial proteinsPeritrophic matrixBacterial biofilm formationGut microbiotaMolecular mechanismsBacterial peptidoglycanPentapeptide chainBiofilm formationIAFGPIxodes scapularis ticksDiverse infectious agentsHuman granulocytic anaplasmosisMicrobiotaProteinAntifreeze glycoproteinsAnaplasma phagocytophilum
2012
Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection
Sukumaran B, Ogura Y, Pedra JH, Kobayashi KS, Flavell RA, Fikrig E. Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection. Pathogens And Disease 2012, 66: 211-219. PMID: 22747758, PMCID: PMC3530031, DOI: 10.1111/j.1574-695x.2012.01001.x.Peer-Reviewed Original ResearchConceptsRip2-deficient miceHuman granulocytic anaplasmosisNOD-like receptorsPhagocytophilum infectionTick-borne infectious diseaseNOD1/NOD2Obligate intracellular bacterium Anaplasma phagocytophilumInflammatory protein-2Host immune responseInnate immune pathwaysProtein 2Anaplasma phagocytophilum infectionHuman primary neutrophilsBacterium Anaplasma phagocytophilumHigh bacterial loadWild-type controlsImmune controlIL-12Immune clearanceImmune responseImmune pathwaysHost responseKC responsesHost defenseInfectious diseasesAnaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells
Ojogun N, Kahlon A, Ragland SA, Troese MJ, Mastronunzio JE, Walker NJ, VieBrock L, Thomas RJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells. Infection And Immunity 2012, 80: 3748-3760. PMID: 22907813, PMCID: PMC3486060, DOI: 10.1128/iai.00654-12.Peer-Reviewed Original ResearchConceptsMammalian host cellsHuman granulocytic anaplasmosisHost cellsHL-60 cellsA. phagocytophilum organismsExtracellular domainP-selectin glycoprotein-1Outer Membrane Protein ASialylated glycoproteinsA. phagocytophilum infectionA. phagocytophilum-infected ticksN-terminal regionMembrane protein AObligate intracellular bacteriumAmino acids 19HGA patientsPhagocytophilum infectionInfectionTransmission feedingGlutathione S-transferaseGranulocytic anaplasmosisIntracellular bacteriumGlycoprotein 1Anaplasma phagocytophilumA. phagocytophilumIxodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey role
2010
Anaplasma phagocytophilum AptA modulates Erk1/2 signalling
Sukumaran B, Mastronunzio JE, Narasimhan S, Fankhauser S, Uchil PD, Levy R, Graham M, Colpitts TM, Lesser CF, Fikrig E. Anaplasma phagocytophilum AptA modulates Erk1/2 signalling. Cellular Microbiology 2010, 13: 47-61. PMID: 20716207, PMCID: PMC3005019, DOI: 10.1111/j.1462-5822.2010.01516.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilum infectionPhagocytophilum infectionCommon tick-borne diseasesHuman granulocytic anaplasmosisActivation of ERK1/2ERK1/2 mitogen-activated protein kinasesA. phagocytophilum survivalPolymorphonuclear leucocytesMitogen-activated protein kinaseHuman neutrophilsObligate intracellular pathogensGranulocytic anaplasmosisIntracellular pathogensTick-borne diseasesInfectionERK1/2 activationAnaplasma phagocytophilumVimentinSurvivalActivationBacterial inclusionsHost proteinsIntermediate filament protein vimentinVirulence proteinsProtein vimentinFucosylation enhances colonization of ticks by Anaplasma phagocytophilum
Pedra JH, Narasimhan S, Rendić D, DePonte K, Bell‐Sakyi L, Wilson IB, Fikrig E. Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum. Cellular Microbiology 2010, 12: 1222-1234. PMID: 20331643, PMCID: PMC3250644, DOI: 10.1111/j.1462-5822.2010.01464.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilumAnaplasma phagocytophilumHuman granulocytic anaplasmosisBacterium Anaplasma phagocytophilumGranulocytic anaplasmosisPathological processesTick feedingPhagocytophilumMicrobial pathogenesisNovel mechanismPathogen colonizationTick cellsFucosylated structuresTicksPathogen invasionPathogenesisSEASONAL PREVALENCE OF SERUM ANTIBODIES TO WHOLE CELL AND RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN WHITE-TAILED DEER IN CONNECTICUT
Magnarelli LA, Williams SC, Fikrig E. SEASONAL PREVALENCE OF SERUM ANTIBODIES TO WHOLE CELL AND RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN WHITE-TAILED DEER IN CONNECTICUT. Journal Of Wildlife Diseases 2010, 46: 781-790. PMID: 20688684, DOI: 10.7589/0090-3558-46.3.781.Peer-Reviewed Original ResearchConceptsRecombinant antigensInfected Ixodes scapularis ticksCoexistence of antibodiesAnaplasma phagocytophilumRespective causative agentsTick-borne infectionsEnzyme-linked immunosorbent assayIndirect fluorescent antibodyHuman granulocytic anaplasmosisPolyvalent enzyme-linked immunosorbent assaysIxodes scapularis ticksWhole blood samplesAntibody titersCurrent infectionWhole-cell B. burgdorferiBorrelia burgdorferi sensu strictoSerum antibodiesTotal antibodyBlood samplesHigher antibodyBurgdorferi sensu strictoSpecific recombinant antigensLyme borreliosisDeer seraImmunosorbent assay
2008
Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function
Thomas V, Samanta S, Fikrig E. Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function. Infection And Immunity 2008, 76: 4905-4912. PMID: 18765732, PMCID: PMC2573316, DOI: 10.1128/iai.00851-08.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumCathepsin LCathepsinsCysteine EndopeptidasesEhrlichiosisElectrophoretic Mobility Shift AssayGene Expression Regulation, BacterialHL-60 CellsHomeodomain ProteinsHumansImmunoblottingImmunoprecipitationNeutrophilsNuclear ProteinsRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsConceptsA. phagocytophilum infectionPhagocytophilum infectionCathepsin L activityNeutrophil functionA. phagocytophilumL activityHuman neutrophil peptides 1Polymorphonuclear leukocyte functionNeutrophil peptide-1Human granulocytic anaplasmosisTherapeutic optionsNeutrophil defenseLeukocyte functionCathepsin LPeptide-1InfectionObligate intracellular pathogensMarked reductionGranulocytic anaplasmosisIntracellular pathogensCDP activityHost oxidative burstAnaplasma phagocytophilumPhagocytophilumOxidative burst
2007
Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection
Thomas V, Fikrig E. Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. Cellular Microbiology 2007, 9: 1730-1737. PMID: 17346310, DOI: 10.1111/j.1462-5822.2007.00908.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumPSGL-1Non-antibiotic strategiesHuman granulocytic anaplasmosisA. phagocytophilum infectionA. phagocytophilum-infected cellsTick-borne agentsPolymorphonuclear leucocytesPromyelocytic cell linePhagocytophilum infectionObligate intracellular pathogensInfectionTyrosine phosphorylationIntracellular pathogensGranulocytic anaplasmosisCell linesROCK1SykPhagocytophilumPhosphorylationNeutrophilsLeucocytesAntibodies
2005
Infection with Anaplasma phagocytophilum Inhibits Proliferation and Differentiation of Myeloid Progenitors: New Insight into Infection-Related Pancytopenia.
Gaines P, Thomas V, Fikrig E, Berliner N. Infection with Anaplasma phagocytophilum Inhibits Proliferation and Differentiation of Myeloid Progenitors: New Insight into Infection-Related Pancytopenia. Blood 2005, 106: 3065. DOI: 10.1182/blood.v106.11.3065.3065.Peer-Reviewed Original ResearchHuman granulocytic anaplasmosisBone marrow progenitorsStem cell factorMarrow progenitorsA. phagocytophilumG-CSFMyeloid progenitorsCell linesObligate intracellular bacterium Anaplasma phagocytophilumOccurrence of thrombocytopeniaPeripheral blood neutrophilsFatal tick-borne diseaseBacterium Anaplasma phagocytophilumBone marrow cellsMarrow suppressionTick-borne diseaseCell line modelsClinical symptomsPhagocyte respiratory burstHematologic abnormalitiesInfection causesBlood neutrophilsCytokine secretionInhibition of apoptosisInfected individualsEffects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels
Carlyon JA, Ryan D, Archer K, Fikrig E. Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels. Infection And Immunity 2005, 73: 7629-7636. PMID: 16239567, PMCID: PMC1273867, DOI: 10.1128/iai.73.11.7629-7636.2005.Peer-Reviewed Original ResearchConceptsFerritin protein levelsProtein levelsHL-60 cellsA. phagocytophilumAnaplasma phagocytophilumSerum-opsonized zymosanHuman granulocytic anaplasmosisA. phagocytophilum infectionInfected HL-60 cellsTime-dependent mannerObligate intracellular bacteriumFerritin levelsInfected miceA. phagocytophilum-infected miceMajor intracellular iron storage proteinFerritin heavy chainHuman promyelocytic HL-60 cellsNADPH oxidase assemblyNeutrophilsPromyelocytic HL-60 cellsMRNA expressionPhagocytophilum infectionIntracellular pathogensGranulocytic anaplasmosisIntracellular bacterium
2004
CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis
Scorpio DG, Akkoyunlu M, Fikrig E, Dumler JS. CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis. MSphere 2004, 11: 963-968. PMID: 15358660, PMCID: PMC515272, DOI: 10.1128/cdli.11.5.963-968.2004.Peer-Reviewed Original ResearchConceptsHuman granulocytic anaplasmosisControl miceGranulocytic anaplasmosisC3H-scid miceInfected cellsTissue loadsObligate intracellular bacteriumNeutrophil recruitmentNeutrophil secretionAntibody blockadeChemokine inductionHepatic pathologyLiver histopathologyInterleukin-8Tissue injuryMouse modelControl animalsDay 14Intracellular bacteriumMiceInfectionAnaplasma phagocytophilumA. phagocytophilumHistopathologyNeutrophils