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.

中文翻译：

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Caspase-11抵消了巨噬细胞中线粒体ROS介导的金黄色葡萄球菌清除。

耐甲氧西林金黄色葡萄球菌（MRSA）由于对抗生素的耐药性增加而日益引起人们的健康关注。作为兼职的细胞内病原体，MRSA能够在包括巨噬细胞在内的专业吞噬细胞内持续存在。在这里，我们确定了CASP11在促进鼠巨噬细胞内MRSA存活中的作用。我们表明，MRSA积极阻止线粒体募集到它们所居住的液泡附近，以避免细胞内死亡。这个过程需要CASP11，因为它的缺乏使含有MRSA的液泡与线粒体的结合增加。抗霉素A（Ant A）对线粒体超氧化物的诱导改善了casp11-/-细胞中MRSA的根除，而线粒体保留在细菌附近。在WT巨噬细胞中，Ant A不会影响MRSA持久性。当肌动蛋白解聚剂细胞松弛素D阻止线粒体解离时，蚂蚁A有效地降低了MRSA数量。此外，CASP11的缺失会导致CASP1，IL-1β和CASP7的切割减少，以及CXCL1 / KC的产生减少。我们的研究为CASP11在促进革兰氏阳性细菌的持久性中提供了新的作用。