Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections.
Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections.
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DOI：
10.1371/journal.ppat.1005026
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发表时间：
2015-07
期刊：
影响因子：
6.7
通讯作者：
Bae T
中科院分区：
文献类型：
--
作者：
Cho H;Jeong DW;Liu Q;Yeo WS;Vogl T;Skaar EP;Chazin WJ;Bae T
钙卫蛋白是中性粒细胞中最丰富的胞质蛋白，通过螯合营养金属离子Zn和Mn来抑制金黄色葡萄球菌的生长。在这里，我们发现钙卫蛋白也可以增强SaeRS双组分系统（TCS）的活性，TCS是一种在S.金黄色。SaeRS TCS的活性被血液或中性粒细胞颗粒中发现的某些二价离子抑制;然而，钙卫蛋白的锌结合形式缓解了这种抑制。在葡萄球菌与小鼠中性粒细胞相遇或小鼠腹膜腔葡萄球菌感染期间，钙卫蛋白增加SaeRS TCS的活性以及促炎细胞因子（如IL-1β和TNF-α）的产生，导致小鼠死亡率升高。这些结果表明，在一定条件下，钙卫蛋白可以被S。金黄色葡萄球菌增加细菌毒力和宿主死亡率。 金黄色葡萄球菌是引起皮肤感染和多种危及生命的疾病如肺炎、败血症和中毒性休克综合征的重要人类病原体。以往的研究表明，S。宿主抗菌蛋白钙卫蛋白（calprotectin）抑制了金黄色葡萄球菌在大肠杆菌中的生长，钙卫蛋白从细菌利用中螯合Zn和Mn。在细菌感染过程中，钙卫蛋白也在促炎细胞因子的产生中起重要作用。虽然钙卫蛋白的抗菌活性已经得到了很好的定义，但尚不清楚钙卫蛋白的促炎特性如何影响葡萄球菌感染。在这项研究中，我们发现钙卫蛋白的锌结合特性增加了沙门氏菌的致病潜力。金黄色葡萄球菌中SaeRS双组分系统的活性。金黄色。我们还发现，在某些感染条件下，钙卫蛋白的促炎特性对宿主的存活是相当不利的。研究结果表明，该蛋白是一种重要的抗菌蛋白，可被S.金黄色葡萄球菌使细菌成为更有效的病原体，并提供了宿主和细菌病原体之间复杂的拔河比赛的例子。
Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression. During staphylococcal encounter with murine neutrophils or staphylococcal infection of the murine peritoneal cavity, calprotectin increases the activity of the SaeRS TCS as well as the production of proinflammatory cytokines such as IL-1β and TNF-α, resulting in higher murine mortality. These results suggest that, under certain conditions, calprotectin can be exploited by S. aureus to increase bacterial virulence and host mortality. Staphylococcus aureus is an important human pathogen causing skin infections and a variety of life-threatening diseases such as pneumonia, sepsis, and toxic shock syndrome. Previous study showed that the growth of S. aureus in abscesses is suppressed by the host antimicrobial protein calprotectin, which sequesters Zn and Mn from bacterial usage. During bacterial infection, calprotectin also plays an important role in the production of proinflammatory cytokines. Although the antimicrobial activity of calprotectin has been well defined, it is not known how the proinflammatory property of calprotectin affects staphylococcal infection. In this study, we found that the Zn-binding property of calprotectin increases the pathogenic potential of S. aureus by enhancing the activity of the SaeRS two component system in S. aureus. We also found that, under certain infection conditions, the proinflammatory property of calprotectin is rather detrimental to host survival. Our study illustrates that the important antimicrobial protein can be exploited by S. aureus to render the bacterium a more effective pathogen, and provides an example of the intricate tug-of-war between host and a bacterial pathogen.
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影响因子：
6.7
作者：
Achouiti A;Vogl T;Urban CF;Röhm M;Hommes TJ;van Zoelen MA;Florquin S;Roth J;van 't Veer C;de Vos AF;van der Poll T
通讯作者：
van der Poll T
影响因子：
4.4
作者：
Baker, Jonathan;Sitthisak, Sutthirat;Morrissey, Julie A.
通讯作者：
Morrissey, Julie A.
影响因子：
3.1
作者：
BHAKDI, S;MUHLY, M;HUGO, F
通讯作者：
HUGO, F
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：
15.9
作者：
GANZ, T;SELSTED, ME;LEHRER, RI
通讯作者：
LEHRER, RI