Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus.
Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus.
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DOI：
10.1016/j.chom.2011.07.004
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发表时间：
2011-08-18
影响因子：
30.3
通讯作者：
Skaar EP
中科院分区：
文献类型：
--
作者：
Kehl-Fie TE;Chitayat S;Hood MI;Damo S;Restrepo N;Garcia C;Munro KA;Chazin WJ;Skaar EP
通过螯合锰和锌，中性粒细胞蛋白钙卫蛋白在宿主防御细菌和真菌病原体中起着至关重要的作用。然而，钙卫蛋白破坏的基本过程仍然未知。我们报告说，钙卫蛋白通过抑制锰依赖性细菌超氧化物防御，从而增加细菌细胞内的超氧化物水平，提高金黄色葡萄球菌对超氧化物的敏感性。超氧化物歧化酶活性是完整的毒力在一个系统性模型的S。金黄色葡萄球菌感染和钙卫蛋白对葡萄球菌超氧化物防御的破坏增强了嗜中性粒细胞的抗微生物活性，促进了体内清除。钙卫蛋白在两个过渡金属结合位点突变，因此结合锰和锌有缺陷，不会抑制微生物生长，明确地将钙卫蛋白的抗微生物特性与金属螯合联系起来。这些结果表明，钙卫蛋白通过使细菌病原体对宿主免疫效应物更敏感并减少细菌生长而有助于宿主防御。
By sequestering manganese and zinc, the neutrophil protein calprotectin plays a crucial role in host defense against bacterial and fungal pathogens. However, the essential processes disrupted by calprotectin remain unknown. We report that calprotectin enhances the sensitivity of Staphylococcus aureus to superoxide through inhibition of manganese-dependent bacterial superoxide defenses thereby increasing superoxide levels within the bacterial cell. Superoxide dismutase activity is required for full virulence in a systemic model of S. aureus infection and disruption of staphylococcal superoxide defenses by calprotectin augments the antimicrobial activity of neutrophils promoting in vivo clearance. Calprotectin mutated in two transition metal binding sites and therefore defective in binding manganese and zinc does not inhibit microbial growth, unequivocally linking the antimicrobial properties of calprotectin to metal chelation. These results suggest that calprotectin contributes to host defense by rendering bacterial pathogens more sensitive to host immune effectors and reducing bacterial growth.
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影响因子：
7.8
作者：
Kehl-Fie, Thomas E.;Skaar, Eric P.
通讯作者：
Skaar, Eric P.
影响因子：
3.6
作者：
Anjem A;Varghese S;Imlay JA
通讯作者：
Imlay JA
影响因子：
3
作者：
Andreini, Claudia;Bertini, Ivano;Thornton, Janet M.
通讯作者：
Thornton, Janet M.
影响因子：
3.2
作者：
Clements, MO;Watson, SP;Foster, SJ
通讯作者：
Foster, SJ
影响因子：
6.7
作者：
Urban CF;Ermert D;Schmid M;Abu-Abed U;Goosmann C;Nacken W;Brinkmann V;Jungblut PR;Zychlinsky A
通讯作者：
Zychlinsky A