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dc.contributor.authorWinstel, Volker
dc.contributor.authorSchneewind, Olaf
dc.contributor.authorMissiakas, Dominique
dc.date.accessioned2019-12-04T12:33:45Z
dc.date.available2019-12-04T12:33:45Z
dc.date.issued2019-11-12
dc.identifier.citationMBio. 2019 Nov 12;10(6). pii: mBio.02270-19. doi: 10.1128/mBio.02270-19.en_US
dc.identifier.issn2150-7511
dc.identifier.pmid31719177
dc.identifier.doi10.1128/mBio.02270-19
dc.identifier.urihttp://hdl.handle.net/10033/622037
dc.description.abstractStaphylococcus aureus is a deadly pathogen that causes fatal diseases in humans. During infection, S. aureus secretes nuclease (Nuc) and adenosine synthase A (AdsA) to generate cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps which triggers noninflammatory apoptosis in macrophages. In this manner, replicating staphylococci escape phagocytic killing without alerting the immune system. Here, we show that mice lacking caspase-3 in immune cells exhibit increased resistance toward S. aureus Caspase-3-deficient macrophages are resistant to staphylococcal dAdo and gain access to abscess lesions to promote bacterial clearance in infected animals. We identify specific single nucleotide polymorphisms in CASP3 as candidate human resistance alleles that protect macrophages from S. aureus-derived dAdo, raising the possibility that the allelic repertoire of caspase-3 may contribute to the outcome of S. aureus infections in humans.IMPORTANCE Caspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a frequent cause of soft tissue and bloodstream infections. Successful commensalism and virulence can be explained by the secretion of a plethora of immune evasion factors. One such factor, AdsA, destroys phagocytic cells by exploiting the apoptotic pathway. However, human CASP3 variants with loss-of-function alleles shield phagocytes from AdsA-mediated killing. This finding raises the possibility that some caspase-3 alleles may arise from exposure to S. aureus and other human pathogens that exploit the apoptotic pathway for infection.en_US
dc.language.isoenen_US
dc.publisherAmerican Society of Microbiologyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectStaphylococcus aureusen_US
dc.subjectadenosine synthase A (AdsA)en_US
dc.subjectcaspase-3en_US
dc.subjectdeoxyadenosineen_US
dc.subjectneutrophil extracellular traps (NETs)en_US
dc.titleStaphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalmBioen_US
refterms.dateFOA2019-12-04T12:33:46Z
dc.source.journaltitlemBio


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