2019
Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality
Park K, Greenwood-Quaintance K, Cunningham S, Rajagopalan G, Chia N, Jeraldo P, Mandrekar J, Patel R. Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality. Microbial Pathogenesis 2019, 133: 103543. PMID: 31102653, DOI: 10.1016/j.micpath.2019.103543.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsBacteremiaBacterial AdhesionBase SequenceCell ProliferationDrug Resistance, BacterialFemaleHLA-DR3 AntigenHumansImmune EvasionMaleMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicMiddle AgedMinnesotaPolymerase Chain ReactionStaphylococcal InfectionsStaphylococcus aureusSuperantigensVirulenceVirulence FactorsConceptsMethicillin-susceptible S. aureusS. aureus bacteremiaAureus bacteremiaMedical CenterHLA-DR3 transgenic miceStaphylococcus aureus bacteremiaMinnesota Medical CenterLarge medical centerImmune evasion genesVirulence genesVirulence gene profilesNumber of deathsClinical dataClinical valueTransgenic miceClinical practiceIndividual PCR assaysWhole-genome sequencing analysisMortalitySAg genesSurvivorsLack of correlationBacteremiaWGS analysisFunctional assays
2017
Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen
Chowdhary VR, Krogman A, Tilahun AY, Alexander MP, David CS, Rajagopalan G. Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen. The Journal Of Immunology 2017, 198: 4413-4424. PMID: 28468970, PMCID: PMC5471834, DOI: 10.4049/jimmunol.1601991.Peer-Reviewed Original ResearchConceptsDNT cellsDKO miceClass II moleculesΑβ TCRT cellsBacterial superantigensCD8 coreceptorIntact MHC class ILupus-like autoimmune diseaseEnterotoxin BHLA-DQ8 moleculesMHC class II moleculesAnti-nuclear AbsPeripheral T cellsDouble knockout miceMurine MHC class II moleculesMHC class IThymic positive selectionStaphylococcal enterotoxin BCD4/CD8 coreceptorsRegulatory cellsHLA-DR3Splenic CD3WT miceAutoimmune diseases
2015
Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice
Krogman AL, Chowdhary V, Rajagopalan G. Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice. Methods In Molecular Biology 2015, 1396: 109-114. PMID: 26676041, PMCID: PMC4882905, DOI: 10.1007/978-1-4939-3344-0_9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalInfusion Pumps, ImplantableMiceStaphylococcal InfectionsStaphylococcusSuperantigensConceptsStaphylococcal superantigensMini-osmotic pumpsChronic continuous exposureSpectrum of diseaseSystemic effectsAcute exposureChronic exposureImmune systemRecurrent exposureSuperantigensContinuous exposureRobust activationS. aureusStaphylococcus aureusInfusion modelExposureAureusSafe wayDiseaseMiceSuperantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, Krogman A, David C, Pritt B, Patel R, Rajagopalan G. Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model. Toxins 2015, 7: 5308-5319. PMID: 26670252, PMCID: PMC4690136, DOI: 10.3390/toxins7124886.Peer-Reviewed Original ResearchConceptsSystemic immune activationImmune activationT cellsS. aureusSerum IL-17 levelsSystemic immunologic effectsIL-17 levelsSpleens of miceWound infection modelImmunologic effectsInflammatory changesHLA-DR3Wound infectionCommon causeTransgenic miceUninfected woundsDay 8Immune systemClinical implicationsInfection modelMiceSkin woundsWoundsMicrobial challengeStaphylococcus aureusSuperantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia
Chung J, Greenwood-Quaintance K, Karau MJ, Tilahun A, Khaleghi SR, Chowdhary VR, David CS, Patel R, Rajagopalan G. Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia. Journal Of Leukocyte Biology 2015, 98: 271-281. PMID: 25979434, PMCID: PMC4501677, DOI: 10.1189/jlb.4a1214-577rr.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatheter-Related InfectionsCatheters, IndwellingCD4-Positive T-LymphocytesEnterotoxinsGene DeletionHistocompatibility AntigensHumansKidneyLiverLungLymphocyte ActivationMiceMice, TransgenicReceptors, Antigen, T-Cell, alpha-betaSpleenStaphylococcal InfectionsStaphylococcus aureusSuperantigensConceptsS. aureusHLA-DR3 transgenic miceLong intravenous catheterSystemic immune activationSerum cytokine levelsSystemic inflammatory diseaseAbsence of bacteremiaMHC class II moleculesInvasive staphylococcal diseaseToxigenic S. aureusClinical S. aureus isolatesS. aureus isolatesClass II moleculesIsogenic S. aureusCytokine levelsHLA-DR3Immune activationInflammatory diseasesIntravenous cathetersStaphylococcal diseaseRole of SAgsDevice-associated infectionsT cellsClinical consequencesForeign body
2014
Superantigens in Staphylococcus aureus isolated from prosthetic joint infection
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, David C, Mandrekar J, Patel R, Rajagopalan G. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection. Diagnostic Microbiology And Infectious Disease 2014, 81: 201-207. PMID: 25619753, PMCID: PMC4336809, DOI: 10.1016/j.diagmicrobio.2014.11.007.Peer-Reviewed Original ResearchSystemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome
Tilahun AY, Chowdhary VR, David CS, Rajagopalan G. Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome. The Journal Of Immunology 2014, 193: 2919-2930. PMID: 25092888, PMCID: PMC4157092, DOI: 10.4049/jimmunol.1400980.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodiesAntigen-Antibody ComplexEnterotoxinsGlucocorticoid-Induced TNFR-Related ProteinGlucocorticoidsHLA-DR alpha-ChainsHLA-DR beta-ChainsHLA-DR3 AntigenInterferon-gammaInterleukin-17Interleukin-2Lymphocyte ActivationMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicReceptors, Tumor Necrosis FactorShock, SepticStaphylococcal InfectionsSuperantigensT-Lymphocytes, RegulatoryUp-RegulationConceptsToxic shock syndromeEndogenous TregsRegulatory cellsShock syndromeT cellsGlucocorticoid-induced TNFR family-related receptorCommunity-acquired methicillin-resistant strainsEx vivoHLA-DR3 transgenic miceSerum IFN-γ levelsFailure of TregsSystemic inflammatory responseIL-2/T regulatory (Treg) cellsIFN-γ levelsConventional T cellsLife-threatening infectionsMethicillin-resistant strainsT cell activationS. aureus strainsTreg numbersAdoptive transferIL-17Immune activationInflammatory responseThe Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia
Tilahun A, Karau M, Ballard A, Gunaratna M, Thapa A, David C, Patel R, Rajagopalan G. The Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia. Mediators Of Inflammation 2014, 2014: 468285. PMID: 25024509, PMCID: PMC4082930, DOI: 10.1155/2014/468285.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsHLA-DQ8 transgenic miceHeat-killed Staphylococcus aureusToxic shock syndromeStaphylococcal superantigensHLA-DR3Shock syndromeMolecular patternsTransgenic miceS. aureus-derived peptidoglycanSerious S. aureus infectionsCytokine/chemokine responsesLipoteichoic acidStaphylococcal toxic shock syndromeS. aureusLife-threatening systemic diseaseAnti-inflammatory roleT cell expansionS. aureus infectionT cell proliferationToxigenic S. aureusStaphylococcus aureusAdaptive immune systemChemokine responsesSystemic diseaseSuperantigen profiling of Staphylococcus aureus infective endocarditis isolates
Chung J, Karau M, Greenwood-Quaintance K, Ballard A, Tilahun A, Khaleghi S, David C, Patel R, Rajagopalan G. Superantigen profiling of Staphylococcus aureus infective endocarditis isolates. Diagnostic Microbiology And Infectious Disease 2014, 79: 119-124. PMID: 24745820, PMCID: PMC4031024, DOI: 10.1016/j.diagmicrobio.2014.03.009.Peer-Reviewed Original ResearchConceptsSuperantigen genesSplenocyte proliferationS. aureusStaphylococcus aureus infective endocarditisMethicillin-susceptible S. aureusMethicillin-resistant S. aureusInfective endocarditis casesEnzyme-linked immunosorbent assayStaphylococcal enterotoxin AInfective endocarditisEndocarditis casesSuperantigen productionMouse splenocyte proliferationPCR-positive isolatesTSST-1EndocarditisImmunosorbent assayEnterotoxin AStaphylococcus aureusAureusProliferationIsolatesMortalityGenes
2012
Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus
Chowdhary VR, Tilahun AY, Clark CR, Grande JP, Rajagopalan G. Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus. The Journal Of Immunology 2012, 189: 2054-2062. PMID: 22798666, PMCID: PMC3462343, DOI: 10.4049/jimmunol.1201097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensAutoimmune DiseasesCD28 AntigensCD4-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFlow CytometryFluorescent Antibody TechniqueHLA-DQ AntigensHumansInfusions, SubcutaneousLupus Erythematosus, SystemicMiceMice, TransgenicStaphylococcus aureusSuperantigensConceptsSystemic lupus erythematosusT cellsChronic exposureStaphylococcal enterotoxin BLupus erythematosusMouse MHC class II moleculesHLA-DQ8 transgenic miceMultisystem autoimmune inflammatory diseaseEnterotoxin BHLA-DQ8 miceAutoimmune inflammatory diseaseMHC class II moleculesTh1-type cytokinesMini-osmotic pumpsMononuclear cell infiltrationAnti-nuclear AbsClass II moleculesAbsence of diseaseChronic nasalIL-12Inflammatory infiltrateAutoimmune diseasesCell infiltrationInflammatory diseasesPathogenic roleLinezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice
Karau M, Tilahun A, Schmidt S, Clark C, Patel R, Rajagopalan G. Linezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice. Antimicrobial Agents And Chemotherapy 2012, 56: 5401-5405. PMID: 22850509, PMCID: PMC3457354, DOI: 10.1128/aac.01080-12.Peer-Reviewed Original ResearchConceptsHLA class II transgenic miceTransgenic miceDR3 transgenic miceII transgenic miceHuman leukocyte antigenS. aureusC57BL/6 miceLeukocyte antigenStaphylococcus aureus virulenceExperimental pneumoniaImmune systemSuperantigensPneumoniaAureus virulenceMiceBacterial protein synthesis inhibitorsProtein synthesis inhibitorStaphylococcus aureusLinezolidPotent activatorSynthesis inhibitorVancomycinAureusGreater protectionSuperior responseThe impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
Tilahun A, Karau M, Clark C, Patel R, Rajagopalan G. The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. Microbes And Infection 2012, 14: 528-536. PMID: 22273732, DOI: 10.1016/j.micinf.2012.01.001.Peer-Reviewed Original ResearchConceptsStaphylococcal superantigensT cell activationChemokine levelsCell activationSystemic inflammatory response syndromeDR3 transgenic miceEfficacy of tacrolimusInflammatory response syndromeHuman leukocyte antigenImpact of tacrolimusPotent immunosuppressive agentPost-exposure treatmentT cell proliferationS. aureus strainsSystemic cytokinesGut dysfunctionSerum cytokinesResponse syndromeImmunosuppressive agentsLeukocyte antigenSystemic pathologyTacrolimusLethal pneumoniaPneumoniaTransgenic mice
2011
Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB
Tilahun M, Kwan A, Natarajan K, Quinn M, Tilahun A, Xie C, Margulies D, Osborne B, Goldsby R, Rajagopalan G. Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB. PLOS ONE 2011, 6: e27203. PMID: 22102880, PMCID: PMC3216929, DOI: 10.1371/journal.pone.0027203.Peer-Reviewed Original ResearchConceptsToxic shock syndromeLethal toxic shock syndromeHLA-DR3 transgenic miceStaphylococcal enterotoxin BChimeric human-mouse antibodyShock syndromeT cellsVivo protectionTransgenic micePartial protectionComplete protectionLethal dosesT cell populationsClass II MHCSignificant partial protectionAnti-SEB antibodiesHuman T cellsOnly partial protectionInflammatory cytokinesClinical safetyII MHCB antibodiesVivo modelChimeric antibodyEnterotoxin BInterferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome
Tilahun A, Holz M, Wu T, David C, Rajagopalan G. Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome. PLOS ONE 2011, 6: e16764. PMID: 21304813, PMCID: PMC3033413, DOI: 10.1371/journal.pone.0016764.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTransgenic miceShock syndromePathogenesis of TSSSmall intestineLethal toxic shock syndromeHLA-DR3 transgenic miceSystematic histopathological examinationSystemic cytokine stormMultiple organ dysfunctionRobust T cell activationSevere inflammatory changesSmall bowel pathologyT cell expansionAnti-inflammatory propertiesSignificant pathological changesT cell activationIFN-γ geneGut permeabilityCytokine stormSEB challengeBowel pathologyInflammatory changesOrgan dysfunctionIntestinal pathology
2010
Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation
Tilahun A, Theuer J, Patel R, David C, Rajagopalan G. Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation. Molecular Therapy 2010, 18: 1143-1154. PMID: 20372109, PMCID: PMC2889741, DOI: 10.1038/mt.2010.53.Peer-Reviewed Original ResearchConceptsToxic shock syndromeStaphylococcal enterotoxin BNF-kappaB activationSystemic inflammationSerum levelsBacterial superantigensKappaB activationElevated TNF-alpha levelsTNF-alpha levelsAcute liver failureProteasome inhibitorsSevere systemic inflammationNuclear factor-kappaBSerum biochemical parametersTNF-alpha-induced cell deathSerum TNFLiver failureHistopathological findingsUntreated miceShock syndromeProphylactic useMurine modelImportant cytokineBortezomibFactor-kappaB
2009
Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor
Rajagopalan G, Tilahun A, Asmann Y, David C. Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor. Physiological Genomics 2009, 37: 279-293. PMID: 19336531, PMCID: PMC2685500, DOI: 10.1152/physiolgenomics.90385.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBoronic AcidsBortezomibCytokinesEnterotoxinsGene Expression ProfilingGene Expression RegulationHLA-DR alpha-ChainsHLA-DR AntigensInflammation MediatorsMiceMice, TransgenicOligonucleotide Array Sequence AnalysisProtease InhibitorsPyrazinesReceptors, ChemokineReceptors, CytokineSignal TransductionSuperantigensConceptsToxic shock syndromePathogenesis of TSSStaphylococcal enterotoxin BBacterial superantigen staphylococcal enterotoxin BSuperantigen staphylococcal enterotoxin BEnterotoxin BAdministration of bortezomibAnti-inflammatory mediatorsTh17-type cytokinesProteasome inhibitorsCytokines/chemokinesSerious systemic illnessTransgenic mouse modelSuitable animal modelEarly gene expression changesNF-kappaB pathwaySystemic illnessSerum levelsShock syndromeImmunoregulatory cytokinesBacterial superantigensCC chemokinesMouse modelVivo administrationAnimal models
2008
CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK
Rajagopalan G, Asmann Y, Lytle A, Tilahun A, Theuer J, Smart M, Patel R, David C. CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK. Shock 2008, 30: 721-728. PMID: 18496243, DOI: 10.1097/shk.0b013e31817048f7.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTherapeutic inhibitionAcute systemic inflammatory responseSevere toxic shock syndromeCytokine/chemokine productionT-cell activation/proliferationPotent T cell activatorsStrong immune activationMultiple organ dysfunctionSystemic inflammatory responseCOX-2 pathwayTransgenic mouse modelActivation/proliferationT cell activatorsT cell activationAgent of bioterrorismOrgan dysfunctionChemokine productionImmune activationFamily of exotoxinsShock syndromeEffective therapyInflammatory responseMicroarray-based gene expression profilingCOX-2
2007
Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice
Rajagopalan G, Polich G, Sen M, Singh M, Epstein B, Lytle A, Rouse M, Patel R, David C. Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice. HLA 2007, 71: 135-145. PMID: 18086265, DOI: 10.1111/j.1399-0039.2007.00986.x.Peer-Reviewed Original ResearchConceptsStreptococcal mitogenic exotoxin ZClass II moleculesHLA class II moleculesHLA-DQ6HLA-DQ8Transgenic miceBacterial superantigensImmune responseHLA class II transgenic miceHLA-DQ8 transgenic miceHuman leukocyte antigen (HLA) class II moleculesHLA class II allelesToxic shock syndrome toxin-1II transgenic miceSimilar clinical outcomesHLA-DQ polymorphismStreptococcal pyrogenic exotoxin AHLA class IIVivo immune responseHLA class II polymorphismClass II allelesPyrogenic exotoxin ASyndrome toxin-1Superantigen-mediated diseasesClass II polymorphism
2006
Comment on: Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation
Rajagopalan G, Patel R, Kaveri S, David C. Comment on: Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation. Journal Of Antimicrobial Chemotherapy 2006, 59: 157-159. PMID: 17071954, DOI: 10.1093/jac/dkl430.Peer-Reviewed Original ResearchIntranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice
Rajagopalan G, Iijima K, Singh M, Kita H, Patel R, David C. Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice. Infection And Immunity 2006, 74: 1284-1296. PMID: 16428778, PMCID: PMC1360368, DOI: 10.1128/iai.74.2.1284-1296.2006.Peer-Reviewed Original ResearchConceptsHLA-DQ8 transgenic miceStaphylococcal enterotoxin BSystemic immune activationAirway inflammationIntranasal exposureTransgenic miceImmune activationIntranasal routeSuperantigen exotoxinsHLA class II transgenic miceHLA-DR3 transgenic miceMajor histocompatibility complex class IIBALB/c miceHistocompatibility complex class IIHLA-DR3 miceII transgenic miceInduces airway inflammationEosinophilic airway inflammationNeutrophilic airway inflammationEosinophilic inflammatory responseStreptococcal pyrogenic exotoxinMurine major histocompatibility complex class IIAirway destructionSerious infectionsC mice