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As a facultative intracellular pathogen, MRSA is capable of persisting within professional phagocytes including macrophages. Here, we identify a role for CASP11 in facilitating MRSA survival within murine macrophages. We show that MRSA actively prevents the recruitment of mitochondria to the vicinity of the vacuoles they reside in to avoid intracellular demise. This process requires CASP11 since its deficiency allows increased association of MRSA\u2010containing vacuoles with mitochondria. The induction of mitochondrial superoxide by antimycin A (Ant A) improves MRSA eradication in\n                    <jats:italic>casp11<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cells, where mitochondria remain in the vicinity of the bacterium. In WT macrophages, Ant A does not affect MRSA persistence. When mitochondrial dissociation is prevented by the actin depolymerizing agent cytochalasin D, Ant A effectively reduces MRSA numbers. Moreover, the absence of CASP11 leads to reduced cleavage of CASP1, IL\u20101\u03b2, and CASP7, as well as to reduced production of CXCL1\/KC. Our study provides a new role for CASP11 in promoting the persistence of Gram\u2010positive bacteria.\n                  <\/jats:p>","DOI":"10.15252\/embr.201948109","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T10:38:18Z","timestamp":1574937498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Caspase\u201011 counteracts mitochondrial ROS\u2010mediated clearance of Staphylococcus aureus in macrophages"],"prefix":"10.1038","volume":"20","author":[{"given":"Kathrin","family":"Krause","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylene","family":"Daily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shady","family":"Estfanous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Badr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwa","family":"Abu Khweek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Hegazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midhun NK","family":"Anne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Klamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail A","family":"Gavrilin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Pancholi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4487-7536","authenticated-orcid":false,"given":"Amal O","family":"Amer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"BFEMBR201948109_CR1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1128\/CMR.10.4.781","volume":"10","author":"HF Chambers","year":"1997","unstructured":"Chambers HF (1997) Methicillin resistance in Staphylococci: molecular and biochemical basis and clinical implications. 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