Caspase-11 counteracts mitochondrial ROS-mediated clearance of Staphylococcus aureus in macrophages.

Kathrin Krause, Kylene Daily, Shady Estfanous, Kaitlin Hamilton, Asmaa Badr, Arwa Abu Khweek, Rana Hegazi, Midhun Nk Anne, Brett Klamer, Xiaoli Zhang, Mikhail A Gavrilin, Vijay Pancholi, Amal O Amer

EMBO reports 2019 Dec 05

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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. © 2019 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Kathrin Krause, Kylene Daily, Shady Estfanous, Kaitlin Hamilton, Asmaa Badr, Arwa Abu Khweek, Rana Hegazi, Midhun Nk Anne, Brett Klamer, Xiaoli Zhang, Mikhail A Gavrilin, Vijay Pancholi, Amal O Amer. Caspase-11 counteracts mitochondrial ROS-mediated clearance of Staphylococcus aureus in macrophages. EMBO reports. 2019 Dec 05;20(12):e48109