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
2014
Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells
Seidman D, Ojogun N, Walker NJ, Mastronunzio J, Kahlon A, Hebert KS, Karandashova S, Miller DP, Tegels BK, Marconi RT, Fikrig E, Borjesson DL, Carlyon JA. Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells. Cellular Microbiology 2014, 16: 1133-1145. PMID: 24612118, PMCID: PMC4115035, DOI: 10.1111/cmi.12286.Peer-Reviewed Original ResearchConceptsGranulocytic anaplasmosisObligate intracellular bacteriumVivo infectionInfectionPhagocytophilum infectionTransmission feedingObligate intracellular pathogensInfected ticksIntracellular pathogensNon-phagocytic cellsIntracellular bacteriumHL-60 cellsHost cell invasionCell invasionAnaplasma phagocytophilumPeptide-specific antiserumOwn uptakeHost cellsAttractive targetInternalization stepMammalian cellsInvasion proteinsSurface proteinsCell morphotypesCells
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
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 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
SEASONAL 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
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 2
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 antibodyMechanisms 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
Effects 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
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 ResearchUSE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER
Magnarelli LA, IJdo JW, Ramakrishnan U, Henderson DW, Stafford KC, Fikrig E. USE OF RECOMBINANT ANTIGENS OF BORRELIA BURGDORFERI AND ANAPLASMA PHAGOCYTOPHILUM IN ENZYME-LINKED IMMUNOSORBENT ASSAYS TO DETECT ANTIBODIES IN WHITE-TAILED DEER. Journal Of Wildlife Diseases 2004, 40: 249-258. PMID: 15362824, DOI: 10.7589/0090-3558-40.2.249.Peer-Reviewed Original Research
2003
Invasion and survival strategies of Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Invasion and survival strategies of Anaplasma phagocytophilum. Cellular Microbiology 2003, 5: 743-754. PMID: 14531890, DOI: 10.1046/j.1462-5822.2003.00323.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumA. phagocytophilumHuman granulocytic ehrlichiosisHostile intracellular environmentTick-borne zoonosisObligate intracellular bacteriumHost neutrophilsNeutrophil adhesionInnate immunityPolymorphonuclear leucocytesAetiological agentGranulocytic ehrlichiosisIntracellular bacteriumNeutrophilsMicrobicidal activityPhagocytophilumHost cellsProteolytic compoundsAcidic lysosomesBacteria-containing phagosomesKey playersLeucocytesImmunityEhrlichiosisPhagocytesMurine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum
Carlyon JA, Akkoyunlu M, Xia L, Yago T, Wang T, Cummings RD, McEver RP, Fikrig E. Murine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum. Blood 2003, 102: 3387-3395. PMID: 12869507, DOI: 10.1182/blood-2003-02-0621.Peer-Reviewed Original ResearchConceptsWild-type miceP-selectin glycoprotein ligand-1Murine neutrophilsCommon tick-borne diseaseAnaplasma phagocytophilumFuc-TIVHuman granulocytic ehrlichiosisPSGL-1 expressionTick-borne diseaseNeutrophil expressionInfection burdenMurine infectionNeutrophilsGranulocytic ehrlichiosisPhagocytophilum infectionMiceHuman neutrophilsSimilar molecular featuresInfectionProductive infectionSialidase treatmentLigand 1PhagocytophilumMolecular featuresFuc-TVII
2002
Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation
Carlyon JA, Chan WT, Galán J, Roos D, Fikrig E. Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation. The Journal Of Immunology 2002, 169: 7009-7018. PMID: 12471136, DOI: 10.4049/jimmunol.169.12.7009.Peer-Reviewed Original ResearchConceptsInfected HL-60 cellsHL-60 cellsAnaplasma phagocytophilaMRNA expressionNADPH oxidaseRetinoic acid-differentiated HL-60 cellsBacterial intracellular survivalHuman granulocytic ehrlichiosisNADPH oxidase activityNADPH oxidase activationQuantitative RT-PCRCMV immediate-early promoterInfected neutrophilsEtiologic agentGranulocytic ehrlichiosisRT-PCR analysisA. phagocytophilaIntracellular survivalSuperoxide productionOxidase activationNeutrophilsProtein expressionRT-PCRImmediate early promoterH postinfectionDifferential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis
IJdo JW, Wu C, Telford SR, Fikrig E. Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2002, 70: 5295-5298. PMID: 12183586, PMCID: PMC128253, DOI: 10.1128/iai.70.9.5295-5298.2002.Peer-Reviewed Original ResearchConceptsP44 geneDifferential expressionHuman granulocytic ehrlichiosisGene familyAntigenic variationHGE bacteriaTransmission feedingGranulocytic ehrlichiosisGenesHypervariable regionInfected C3H miceP44 expressionTick transmissionExpressionSCID miceC3H miceHGE infectionMurine modelInfected ticksSalivary glandsNymphal ticksMiceTicksEhrlichiosisBacteria