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Updated: Jan 5, 2026
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Caspase-11 counteracts mitochondrial ROS-mediated clearance of Staphylococcus aureus in macrophages
Kathrin Krause1, Kylene Daily1, Shady Estfanous1
1Department of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State University, Columbus, OH, USA.
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.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) survives in macrophages by preventing mitochondrial association, a process dependent on CASP11. Inhibiting this pathway enhances MRSA eradication, revealing a novel role for CASP11 in bacterial persistence.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat due to antibiotic resistance.
- MRSA is an intracellular pathogen that can survive within macrophages, professional phagocytes.
Purpose of the Study:
- To investigate the role of CASP11 in MRSA survival within murine macrophages.
- To elucidate the mechanisms by which MRSA evades intracellular killing.
Main Methods:
- Utilized murine macrophages and MRSA infection models.
- Assessed the association of MRSA-containing vacuoles with mitochondria.
- Investigated the effect of antimycin A (Ant A) and cytochalasin D on MRSA survival.
- Measured caspase cleavage and cytokine production.
Main Results:
- MRSA actively prevents mitochondrial recruitment to its vacuole, requiring CASP11.
- CASP11 deficiency enhances mitochondrial association with MRSA vacuoles.
- Antimycin A-induced mitochondrial superoxide aids MRSA eradication in CASP11-deficient cells.
- CASP11 absence reduces caspase-1, IL-1β, and caspase-7 cleavage, and CXCL1/KC production.
Conclusions:
- CASP11 promotes MRSA persistence by facilitating the dissociation of mitochondria from MRSA-containing vacuoles.
- Targeting this CASP11-mediated pathway offers a potential strategy for MRSA eradication.
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