Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 1161 21(st) Avenue South, MCN A-5102, Nashville, TN 37232, USA.
Department of Microbiology, Microbial Pathogenesis Program, New York University School of Medicine, New York, NY 10016, USA.
Cell Host Microbe. 2017 Oct 11;22(4):531-542.e8. doi: 10.1016/j.chom.2017.08.009. Epub 2017 Sep 21.
Diet, and specifically dietary metals, can modify the risk of infection. However, the mechanisms by which manganese (Mn), a common dietary supplement, alters infection remain unexplored. We report that dietary Mn levels dictate the outcome of systemic infections caused by Staphylococcus aureus, a leading cause of bacterial endocarditis. Mice fed a high Mn diet display alterations in Mn levels and localization within infected tissues, and S. aureus virulence and infection of the heart are enhanced. Although the canonical mammalian Mn-sequestering protein calprotectin surrounds staphylococcal heart abscesses, calprotectin is not released into the abscess nidus and does not limit Mn in this organ. Consequently, excess Mn is bioavailable to S. aureus in the heart. Bioavailable Mn is utilized by S. aureus to detoxify reactive oxygen species and protect against neutrophil killing, enhancing fitness within the heart. Therefore, a single dietary modification overwhelms vital host antimicrobial strategies, leading to fatal staphylococcal infection.
饮食,特别是饮食中的金属,可以改变感染的风险。然而,锰(Mn)作为一种常见的膳食补充剂,改变感染的机制仍未被探索。我们报告说,膳食 Mn 水平决定了金黄色葡萄球菌(一种引起细菌性心内膜炎的主要原因)引起的全身感染的结果。用高 Mn 饮食喂养的小鼠显示出感染组织内 Mn 水平和定位的改变,金黄色葡萄球菌的毒力和心脏感染增强。尽管经典的哺乳动物 Mn 螯合蛋白钙卫蛋白包围着金黄色葡萄球菌心脏脓肿,但钙卫蛋白不会释放到脓肿核心,也不会限制该器官中的 Mn。因此,过量的 Mn 对心脏中的金黄色葡萄球菌是生物可利用的。生物可利用的 Mn 被金黄色葡萄球菌用来解毒活性氧并抵抗中性粒细胞的杀伤,从而增强了在心脏中的适应性。因此,单一的饮食改变压倒了重要的宿主抗菌策略,导致致命的金黄色葡萄球菌感染。