TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells.

TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells.
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DOI:
10.1007/s11010-011-0840-3
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发表时间:
2011-09
影响因子:
4.3
通讯作者:
Reddy, Jay
Reddy, Jay
中科院分区:
生物学3区
文献类型:
--
作者:
Massilamany, Chandirasegaran;Gangaplara, Arunakumar;Gardner, Donald J.;Musser, James M.;Steffen, David;Somerville, Greg A.;Reddy, Jay

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在小鼠软组织感染模型中,金黄色葡萄球菌三羧酸(TCA)循环的灭活延迟了皮肤溃疡的消退。在这项研究中,观察到皮肤病变感染野生型或同基因乌头酸酶突变体S。金黄色葡萄球菌菌株含有相当的炎性浸润,表明延迟的消退与免疫细胞的募集无关。这些观察结果使我们假设葡萄球菌代谢可以调节宿主的免疫反应。利用RAW 264.7细胞体外模型系统,作者观察到与S.与暴露于野生型细菌的那些细胞相比,金黄色葡萄球菌顺乌头酸酶突变株产生显著较低量的一氧化氮(NO·)和诱导型一氧化氮合酶。尽管NO·合成减少,抗原呈递和共刺激分子的表达在与野生型和与顺乌头酸酶突变体细菌培养的细胞中是相似的。这些数据表明,葡萄球菌可以逃避先天免疫反应,并通过改变其代谢来潜在地增强其在感染宿主中的生存能力。这也可以解释临床S.金黄色葡萄球菌分离株。
Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO•) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO• synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.
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