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The Pseudomonas aeruginosa virulence factor ExoU activates pyroptosis
Organization UNIVERSITY OF SOUTH ALABAMALocation MOBILE, UNITED STATESPosted 1 Dec 2023Deadline 31 Oct 2025 โ ๏ธ
NIHUS FederalResearch GrantFY2025APF-1ATP-Dependent Proteolysis Factor 1Active SitesAcute Lung InjuryAcute Pulmonary InjuryAirway failureAntibiotic ResistanceApoptosis-Related Cysteine Protease Caspase 1AspartateBacterial ToxinsBypassCASP-1CASP1CASP1 geneCOPDCa2+-Activated ProteaseCalcium-Activated Neutral ProteaseCalcium-Activated Neutral ProteinaseCalcium-Activated ProteaseCalcium-Dependent Neutral ProteaseCalcium-Dependent Neutral ProteinaseCalpainCaspaseCaspase GeneCaspase-1Caspase-1 GeneCausalityCell BodyCell Communication and SignalingCell Culture TechniquesCell DeathCell SignalingCell modelCell-Death ProteaseCellsCellular MatrixCellular injuryCellular modelChronic Obstruction Pulmonary DiseaseChronic Obstructive Lung DiseaseChronic Obstructive Pulmonary DiseaseChronic lung diseaseCombined Modality TherapyCritical IllnessCritically IllCysteineCysteine EndopeptidasesCysteine ProteaseCysteine ProteinasesCystic FibrosisCytolysisCytoskeletal SystemCytoskeletonDataDesminaseDysfunctionEC 3.1.1.4ESKAPEESKAPE pathogensEndothelial CellsEndotheliumEpithelial CellsEsteroproteasesEtiologyFunctional disorderGenesHMG-20Half-CystineHeartHigh Mobility Protein 20HumanICE ProteaseICE-like proteaseIL-1 beta ConvertaseIL-1 beta-Converting EnzymeIL-1BCIL-1b Converting EnzymeIL1B-ConvertaseIL1BCIL1BCEImmune infiltratesImmunocompromisedImmunocompromised HostImmunocompromised PatientImmunosuppressed HostInfectionInflammasomeInflammationInflammatoryIntensive Care UnitsInterleukin 1-B Converting EnzymeInterleukin 1-Beta ConvertaseInterleukin-1 Beta Converting EnzymeInterleukin-1 Converting EnzymeIntoxicationIntracellular Communication and SignalingKnowledgeL-AspartateL-CysteineLeadLecithinase A2LipopolysaccharidesLungLung Respiratory SystemLung damageLysisLytotoxicityMacrophageMediatingMediatorMembraneModelingModern ManMorbidityMorbidity - disease rateMucoviscidosisMultimodal TherapyMultimodal TreatmentMฯNosocomial pneumoniaP aeruginosaP aeruginosa associated pneumoniaP aeruginosa caused pneumoniaP aeruginosa induced pneumoniaP aeruginosa pneumoniaP aeruginosa-associated pneumoniaP aeruginosa-caused pneumoniaP aeruginosa-induced pneumoniaP. aeruginosaP. aeruginosa associated pneumoniaP. aeruginosa caused pneumoniaP. aeruginosa induced pneumoniaP. aeruginosa infectionP. aeruginosa pneumoniaP. aeruginosa-associated pneumoniaP. aeruginosa-caused pneumoniaP. aeruginosa-induced pneumoniaPLA2Papain-Like Cysteine ProteasePathogenesisPathogenicityPathogenicity FactorsPathway interactionsPatientsPb elementPeptidasesPeptide HydrolasesPermeabilityPhospholipase A2Phospholipases APhysiologyPhysiopathologyPneumoniaPositionPositioning AttributePrevalenceProcessProtease GeneProteasesProteinasesProteolytic EnzymesPseudomonas aeruginosaPseudomonas aeruginosa associated pneumoniaPseudomonas aeruginosa caused pneumoniaPseudomonas aeruginosa induced pneumoniaPseudomonas aeruginosa infectionPseudomonas aeruginosa pneumoniaPseudomonas pyocyaneaPublicationsPublishingRecoveryResistance to antibioticsResistant to antibioticsRespiratory FailureRoleScientific PublicationSepsisSeveritiesSignal TransductionSignal Transduction SystemsSignalingT3SSTechnologyTestingType III Secretion SystemType III Secretion System PathwayUbiquitinVirulenceVirulence FactorsVirulentWorkWorld Health Organizationadverse consequenceadverse outcomeantibiotic drug resistanceantibiotic resistantbiological signal transductioncausationcell culturecell culturescell damagecell injurycell typecellular damagechronic obstructive pulmonary disorderchronic pulmonary diseasecombination therapycombined modality treatmentcombined treatmentcystein proteasecystein proteinasecysteine endopeptidasecytotoxicitydamage to cellsdisease causationexoenzymeexperimentexperimental researchexperimental studyexperimentsgene editing methodgene editing methodologygene editing strategygene editing techniquesgene-editing approachhealthcare-associated pneumoniaheavy metal Pbheavy metal leadhospital acquired pneumoniahospital associated pneumoniaimmune cell infiltrateimmunosuppressed patientinducible expressioninducible gene expressioninfected with P. aeruginosainfected with Pseudomonas aeruginosainjury to cellsinnovateinnovationinnovativeintracellular skeletonlecithinase Alung injurymembrane structuremortalitymulti-modal therapymulti-modal treatmentnecrocytosisnovelold ageopportunistic pathogenpathogenpathophysiologypathwaypharmacologicphosphatidasephosphatidolipasephosphatidylcholine 2 acylhydrolasepneumonia therapypneumonia treatmentpulmonary damagepulmonary injurypulmonary tissue damagepulmonary tissue injuryresponsesocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic agent developmenttherapeutic developmenttreat pneumoniatype 3 secretion system
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PROJECT SUMMARY/ABSTRACT
Our recent publications described pathogenic effects of the Pseudomonas aeruginosa type III secretion
system effector ExoU on caspase-1 regulated inflammation. Our new preliminary data indicate that ExoU
bypasses the inflammasome to induce a non-canonical form of caspase-1 activation in lung endothelial cells.
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