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
2013
SERUM ANTIBODIES TO BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN RECAPTURED WHITE-FOOTED MICE
Magnarelli LA, Williams SC, Norris SJ, Fikrig E. SERUM ANTIBODIES TO BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN RECAPTURED WHITE-FOOTED MICE. Journal Of Wildlife Diseases 2013, 49: 294-302. PMID: 23568904, PMCID: PMC3712766, DOI: 10.7589/2012-06-172.Peer-Reviewed Original ResearchConceptsB. microtiA. phagocytophilumB. burgdorferiBabesia microtiSolid-phase enzyme-linked immunosorbent assayAnaplasma phagocytophilumMouse immune systemEnzyme-linked immunosorbent assayIndirect fluorescent antibodyAntibody statusAntibody titersBorrelia burgdorferi sensu strictoSerum antibodiesTotal antibodyAntibody prevalenceNegative statusBurgdorferi sensu strictoImmune systemPatent infectionsEnd pointMiceImmunosorbent assayAntibodiesBorrelia burgdorferiFluorescent antibody
2012
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection. Infection And Immunity 2012, 81: 65-79. PMID: 23071137, PMCID: PMC3536139, DOI: 10.1128/iai.00932-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsBinding SitesCell AdhesionCell Line, TumorEhrlichiaEhrlichiosisGene Expression Regulation, BacterialGlutathione TransferaseHL-60 CellsHumansMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataProtein BindingProtein Structure, TertiaryProteomeSequence Analysis, ProteinTranscription, GeneticUp-RegulationConceptsMammalian host cellsHost cellsReticulate cellsOuter membrane protein candidatesSurface proteinsOuter membrane protein AMembrane protein AA. phagocytophilum-infected ticksObligate intracellular bacteriumA. phagocytophilumGlutathione S-transferaseTranscriptional profilingSurface proteomeC-terminusAffinity purificationFamily AnaplasmataceaeProtein candidatesSelective biotinylationCellular invasionAsp14Transmission feedingAmino acidsS-transferaseIntracellular bacteriumP-selectin glycoprotein ligand-1Anaplasma 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. phagocytophilumPostgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice
Mastronunzio JE, Kurscheid S, Fikrig E. Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice. Journal Of Bacteriology 2012, 194: 2238-2247. PMID: 22389475, PMCID: PMC3347074, DOI: 10.1128/jb.06791-11.Peer-Reviewed Original ResearchConceptsOpen reading frameA. phagocytophilum genomeObligate intracellular bacteriaBlood-feeding arthropodsCell surface proteinsMammalian cell cultureRickettsiales orderUncharacterized proteinsRibosomal proteinsEssential proteinsTranscriptome sequencingBacterial adaptationA. phagocytophilumDNA replicationTick salivary glandsPostgenomic analysisReading frameMammalian hostsAnaplasma phagocytophilumDevelopmental transitionsDC-specific markerIntracellular bacteriaTransmission feedingSurface proteinsProtein
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original Research
2010
Fucosylation 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 invasionPathogenesisAnaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
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
c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection
Pedra JH, Mattner J, Tao J, Kerfoot SM, Davis RJ, Flavell RA, Askenase PW, Yin Z, Fikrig E. c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection. Infection And Immunity 2007, 76: 308-316. PMID: 17998313, PMCID: PMC2223674, DOI: 10.1128/iai.00599-07.Peer-Reviewed Original ResearchConceptsIFN-gamma productionA. phagocytophilum infectionPhagocytophilum infectionIFN-gammaJnk2-null miceNatural killer T cellsA. phagocytophilumKiller T cellsIFN-gamma releaseIFN-gamma secretionGamma interferon productionT cell agonistsAnaplasma phagocytophilum infectionT cellsEarly eradicationGamma interferonInterferon productionInfectionC-Jun NH2-terminal kinase-2Inhibitory effectElevated levelsMiceAnaplasma phagocytophilumPhagocytophilumKinase 2ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection
Pedra JH, Sutterwala FS, Sukumaran B, Ogura Y, Qian F, Montgomery RR, Flavell RA, Fikrig E. ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection. The Journal Of Immunology 2007, 179: 4783-4791. PMID: 17878377, DOI: 10.4049/jimmunol.179.7.4783.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnaplasmaAnaplasmosisAnimalsApoptosis Regulatory ProteinsCalcium-Binding ProteinsCaspase 1Disease SusceptibilityEnzyme ActivationHL-60 CellsHumansInterferon-gammaInterleukin-18Killer Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutPhagocytosisSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryConceptsA. phagocytophilum infectionIFN-gamma productionCaspase-1Phagocytophilum infectionIFN-gammaA. phagocytophilumIFN-gamma levelsNOD-like receptor pathwayIL-18 secretionIFN-gamma-mediated controlCentral adaptor moleculeAnaplasma phagocytophilum infectionVitro restimulationIL-18Peripheral bloodControl animalsReceptor pathwayASC deficiencyInfectionObligate intracellular pathogensIntracellular pathogensAnaplasma phagocytophilumPhagocytophilumAdaptor moleculeCritical roleIL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis
Pedra JH, Tao J, Sutterwala FS, Sukumaran B, Berliner N, Bockenstedt LK, Flavell RA, Yin Z, Fikrig E. IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis. Pathogens And Disease 2007, 50: 401-410. PMID: 17521390, DOI: 10.1111/j.1574-695x.2007.00270.x.Peer-Reviewed Original ResearchConceptsIL-12/23p40Deficient miceT cellsImmune responseHuman anaplasmosisTh1 immune responseIFN-gamma productionDay 6 postinfectionAnaplasma phagocytophilumA. phagocytophilum burdenIL-23Dendritic cellsIL-12Neutrophil numbersIFN-gammaMurine modelMicrobial agonistsPathogen clearanceDependent clearanceInfectious diseasesEarly susceptibilityPathogen eliminationCausative agentA. phagocytophilumIndependent mechanisms
2006
ANTIBODIES TO WHOLE-CELL OR RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN WHITE-FOOTED MICE
Magnarelli LA, Stafford KC, IJdo JW, Fikrig E. ANTIBODIES TO WHOLE-CELL OR RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN WHITE-FOOTED MICE. Journal Of Wildlife Diseases 2006, 42: 732-738. PMID: 17255439, DOI: 10.7589/0090-3558-42.4.732.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumAnimalsAnimals, WildAntibodies, BacterialAntibodies, ProtozoanAntigens, BacterialAntigens, ProtozoanBabesia microtiBabesiosisBorrelia burgdorferiConnecticutEhrlichiosisEnzyme-Linked Immunosorbent AssayLyme DiseasePeromyscusRodent DiseasesSeroepidemiologic StudiesTick-Borne DiseasesConceptsEnzyme-linked immunosorbent assayB. burgdorferiOverall antibody prevalence rateBabesia microtiBorrelia burgdorferiAntibody prevalence ratesAnaplasma phagocytophilumA. phagocytophilumIndirect fluorescent antibodyWhite-footed miceWhole cell antigenTick-infested areasWhole-cell B. burgdorferiCurrent infectionPrevalence ratesMouse serumAntigenImmunosorbent assaySerum samplesRecombinant antigensAntibodiesSerumB. microtiMiceFluorescent antibodyAn Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
Sukumaran B, Narasimhan S, Anderson JF, DePonte K, Marcantonio N, Krishnan MN, Fish D, Telford SR, Kantor FS, Fikrig E. An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands. Journal Of Experimental Medicine 2006, 203: 1507-1517. PMID: 16717118, PMCID: PMC2118316, DOI: 10.1084/jem.20060208.Peer-Reviewed Original ResearchConceptsA. phagocytophilum-infected miceRNA interference-mediated silencingA. phagocytophilumTick salivary proteinsI. scapularis salivary glandsRickettsia-like pathogensTick salivary glandsMammalian hostsGenus RickettsiaAnaplasma phagocytophilumGene expressionSalivary glandsIntracellular organismsArthropodsSalivary proteinsPathogensProteinPhagocytophilumExpressionTicksHuman anaplasmosisSilencingGenesOrganismsAnaplasmaMechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum. Current Opinion In Hematology 2006, 13: 28-33. PMID: 16319684, DOI: 10.1097/01.moh.0000190109.00532.56.Peer-Reviewed Original ResearchConceptsApoptosis differentiation programMitochondrial membrane integrityA. phagocytophilumCaspase-3 activationBacterium altersMolecular machineryVacuolar membraneTranscription factorsDifferentiation programMammalian hostsSecretory vesiclesAnaplasma phagocytophilumCytoplasmic compartmentGene expressionPromoter activityAntiapoptotic genesNADPH oxidase assemblyOxidase assemblyNeutrophil gene expressionHost cellsBacterial uptakeNADPH oxidase componentsMechanisms of evasionMembrane integrityCytochrome b558
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 bacteriumSeroprevalence of antibodies against Borrelia burgdorferi and Anaplasma phagocytophilum in cats.
Magnarelli LA, Bushmich SL, IJdo JW, Fikrig E. Seroprevalence of antibodies against Borrelia burgdorferi and Anaplasma phagocytophilum in cats. American Journal Of Veterinary Research 2005, 66: 1895-9. PMID: 16334946, DOI: 10.2460/ajvr.2005.66.1895.Peer-Reviewed Original ResearchConceptsRecombinant antigensSerum antibodiesB. burgdorferiHealthy catsBorrelia burgdorferiSeroprevalence of antibodiesWestern blot testingAnaplasma phagocytophilumA. phagocytophilumB. burgdorferi antigensWhole cell antigenA. phagocytophilum infectionIndirect fluorescent antibody stainingWestern blot analysisIxodes scapularis ticksSeropositivity rateWhole-cell B. burgdorferiSerum reactivityIll catsFluorescent antibody stainingClinical relevanceSera reactiveSpecific recombinant antigensMost catsOuter surface proteins
2004
Interferon-γ deficiency reveals that 129Sv mice are inherently more susceptible to Anaplasma phagocytophilum than C57BL/6 mice
Wang T, Akkoyunlu M, Banerjee R, Fikrig E. Interferon-γ deficiency reveals that 129Sv mice are inherently more susceptible to Anaplasma phagocytophilum than C57BL/6 mice. Pathogens And Disease 2004, 42: 299-305. PMID: 15477043, DOI: 10.1016/j.femsim.2004.06.001.Peer-Reviewed Original ResearchCXCR2 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