Caspase‐11 counteracts mitochondrial ROS‐mediated clearance of Staphylococcus aureus in macrophages. (21st October 2019)

• Record Type: Journal Article
• Authors: Krause, Kathrin; Daily, Kylene; Estfanous, Shady; Hamilton, Kaitlin; Badr, Asmaa; Abu Khweek, Arwa; Hegazi, Rana; Anne, Midhun NK; Klamer, Brett; Zhang, Xiaoli; Gavrilin, Mikhail A; Pancholi, Vijay; Amer, Amal O
• Is Part Of: EMBO reports. Volume 20:Number 12(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-10-21
• Subjects: caspase‐11 -- macrophages -- mitochondria -- ROS -- Staphylococcus aureus; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201948109
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Methicillin‐resistant Staphylococcus aureus (MRSA) is a growing health concern due to increasing resistance to antibiotics. 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‐containing vacuoles with mitochondria. The induction of mitochondrial superoxide by antimycin A (Ant A) improves MRSA eradication in casp11 −/− 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‐1β, 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‐positive bacteria. Synopsis: Staphylococcus aureus exploits caspase‐11 to dissociate MRSA‐containing vacuoles from mitochondria. Caspase‐11 also promotes inflammasome activation and secretion of IL‐1α, IL‐1β, and CXCL1/KC in response to MRSA infection in macrophages. Methicillin‐resistant Staphylococcus aureus (MRSA) exploits caspase‐11 to promote its persistence. Caspase‐11 is required for the dissociation of mitochondria from MRSA‐containing vacuoles. Mitochondrial ROS contribute to MRSA clearance in the absence of caspase‐11. Abstract : Staphylococcus aureus exploits caspase‐11 to dissociate MRSA‐containing vacuoles from mitochondria. Caspase‐11 also promotes inflammasome activation and secretion of IL‐1α, IL‐1β, and CXCL1/KC in response to MRSA infection in macrophages.