Intracellular Staphylococcus aureus Perturbs the Host Cell Ca+ Homeostasis To Promote Cell Death.

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dc.contributor.authorStelzner, Kathrin
dc.contributor.authorWinkler, Ann-Cathrin
dc.contributor.authorLiang, Chunguang
dc.contributor.authorBoyny, Aziza
dc.contributor.authorAde, Carsten P
dc.contributor.authorDandekar, Thomas
dc.contributor.authorFraunholz, Martin J
dc.contributor.authorRudel, Thomas
dc.contributor.departmentHIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.en_US
dc.date.accessioned2021-01-22T14:48:28Z
dc.date.available2021-01-22T14:48:28Z
dc.date.issued2020-12-15
dc.description.abstractThe opportunistic human pathogen Staphylococcus aureus causes serious infectious diseases that range from superficial skin and soft tissue infections to necrotizing pneumonia and sepsis. While classically regarded as an extracellular pathogen, S. aureus is able to invade and survive within human cells. Host cell exit is associated with cell death, tissue destruction, and the spread of infection. The exact molecular mechanism employed by S. aureus to escape the host cell is still unclear. In this study, we performed a genome-wide small hairpin RNA (shRNA) screen and identified the calcium signaling pathway as being involved in intracellular infection. S. aureus induced a massive cytosolic Ca2+ increase in epithelial host cells after invasion and intracellular replication of the pathogen. This was paralleled by a decrease in endoplasmic reticulum Ca2+ concentration. Additionally, calcium ions from the extracellular space contributed to the cytosolic Ca2+ increase. As a consequence, we observed that the cytoplasmic Ca2+ rise led to an increase in mitochondrial Ca2+ concentration, the activation of calpains and caspases, and eventually to cell lysis of S. aureus-infected cells. Our study therefore suggests that intracellular S. aureus disturbs the host cell Ca2+ homeostasis and induces cytoplasmic Ca2+ overload, which results in both apoptotic and necrotic cell death in parallel or succession.IMPORTANCE Despite being regarded as an extracellular bacterium, the pathogen Staphylococcus aureus can invade and survive within human cells. The intracellular niche is considered a hideout from the host immune system and antibiotic treatment and allows bacterial proliferation. Subsequently, the intracellular bacterium induces host cell death, which may facilitate the spread of infection and tissue destruction. So far, host cell factors exploited by intracellular S. aureus to promote cell death are only poorly characterized. We performed a genome-wide screen and found the calcium signaling pathway to play a role in S. aureus invasion and cytotoxicity. The intracellular bacterium induces a cytoplasmic and mitochondrial Ca2+ overload, which results in host cell death. Thus, this study first showed how an intracellular bacterium perturbs the host cell Ca2+ homeostasis.en_US
dc.identifier.citationmBio. 2020 Dec 15;11(6):e02250-20. doi: 10.1128/mBio.02250-20.en_US
dc.identifier.doi10.1128/mBio.02250-20
dc.identifier.eissn2150-7511
dc.identifier.journalmBioen_US
dc.identifier.pmid33323513
dc.identifier.urihttp://hdl.handle.net/10033/622695
dc.language.isoenen_US
dc.publisherASMen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.source.countryUnited States
dc.source.issue6
dc.source.journaltitlemBio
dc.source.volume11
dc.subjectStaphylococcus aureusen_US
dc.subjectcalcium signaling pathwayen_US
dc.subjectcell deathen_US
dc.subjectfacultatively intracellular pathogensen_US
dc.titleIntracellular Staphylococcus aureus Perturbs the Host Cell Ca+ Homeostasis To Promote Cell Death.en_US
dc.typeArticleen_US
dspace.entity.typePublication
refterms.dateFOA2021-01-22T14:48:29Z
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