The Role of Staphylococcus aureus SasD in Lung
The Role of Staphylococcus aureus SasD in Lung
批准号:
10748089
负责人:
John F Alcorn
金额:
$57.16万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-23 至 2027-06-30
关键词:
AddressAdherenceAdhesionsAlveolar MacrophagesAnimal ModelAntibiotic TherapyAntibioticsAntigen PresentationAttenuatedBacteriaBacterial AdhesionBacterial Attachment SiteBindingCOVID-19 pandemicCell Culture TechniquesCell DeathCell WallCell-Matrix JunctionCellsClinicalDataEnzymesEpithelial AttachmentEpithelial CellsEpitheliumExtracellular Matrix ProteinsFutureGenomeGrowthHumanImaging TechniquesImmuneImmune systemImmunityIn VitroIndividualInfectionInflammasomeInflammationInflammatoryInfluenzaInjuryInterleukin-1 betaLaboratoriesLungLung infectionsMacrophageMediatingMembrane ProteinsMonoclonal AntibodiesMusMutationOrganoidsPathogenesisPathway interactionsPhagocytesPhagolysosomePneumoniaPredispositionPreventionProductionProtein FamilyProteinsPublishingPulmonary InflammationRegulationResearchRoleSignal TransductionStainsStaphylococcus aureusStaphylococcus aureus infectionSystemT-LymphocyteTestingTherapeuticVaccine DesignVaccinesViralVirulenceVirulence FactorsVirus DiseasesWorkattenuationbacterial resistancecommunity acquired pneumoniacytokineexperimental studyhuman modelhumanized mouseimmunoregulationin vitro Assayin vivoinfluenza infectioninfluenzaviruslung injurymembermethicillin resistant Staphylococcus aureusmortalitymutantnew therapeutic targetnovelpre-clinicalprotein expressionrecruitsortasesuperinfectiontherapeutic evaluationtherapeutic targettherapy designtooluptake
中文摘要
总结
英文摘要
SUMMARY
Despite intense research focus, Staphylococcus aureus has remained an important cause of both community
acquired pneumonia and viral-related super-infections. The field has recently determined host mediated
mechanisms induced by S. aureus that drive lung infection and injury. In the context of preceding influenza
infection, our group and many others have delineated aberrant immune pathway regulation as key drivers of S.
aureus susceptibility and pathogenesis. In addition to host mediated interactions, S. aureus expresses a number
of secreted and cell wall virulence factors that have not been fully characterized in pulmonary infection. We
performed a transposon mutant screen of S. aureus cell wall anchored proteins in pulmonary infection and super-
infection in mice. This screen revealed a novel S. aureus virulence factor, SasD, which is required for lung
inflammation, injury, and mortality. SasD was also required for lung epithelial cell attachment and inflammatory
cytokine induction by macrophages. In this application, we hypothesize that S. aureus SasD is a critical virulence
factor in pulmonary infection, which mediates bacterial adherence to the lung stroma and interactions with
primary lung phagocytes. We will test this hypothesis with two independent, but related Aims; 1) investigate the
role of SasD in bacterial adhesion to lung epithelial cells and in vivo growth in the lung, 2) examine the role of
SasD in mediating S. aureus interaction with pulmonary phagocytes and the impact on lung inflammation. We
will determine the context dependent roles of S. aureus SasD in single and influenza super-infection. Further,
we will utilize cutting edge tools to determine these interactions in human and mouse systems. Data generated
in this project will inform upon focusing on S. aureus SasD at a potential therapeutic or vaccine target in
pulmonary infections.
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