Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) of Staphylococcus aureus is essential for the virulence independent of LuxS/AI-2 system

Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) of Staphylococcus aureus is essential for the virulence independent of LuxS/AI-2 system
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金黄色葡萄球菌的甲硫腺苷/S-腺苷高半胱氨酸核苷酶 (Pfs) 对于独立于 LuxS/AI-2 系统的毒力至关重要

DOI:
10.1016/j.ijmm.2013.03.004
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发表时间:
2013-05-01
影响因子:
4.1
通讯作者:
Sun, Baolin
Sun, Baolin
中科院分区:
医学3区
文献类型:
--
作者:
Bao, Yan;Li, Yajuan;Sun, Baolin

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金黄色葡萄球菌是社区和医院环境中感染性发病率和死亡率的主要原因。该细菌继续引起多种侵入性的、危及生命的感染,如肺炎、心内膜炎和败血症。甲基硫代腺苷/S-腺苷高半胱氨酸核苷酶(Pfs)被预测为参与甲基化反应、多胺合成、维生素合成和群体感应途径的重要酶。我们首次证明了Pfs对S.金黄色。的pfs突变株,与同基因野生型相比,显示出细胞外蛋白酶的生产减少,这是与sspABC操纵子的表达和aur表达的适度减少的显着减少。脓毒症和皮下脓肿的小鼠模型表明,与同基因野生型相比,pfs突变株显示出高度受损的毒力。在斑马鱼胚胎透明系统中的实时分析表明,pfs突变株毒力的降低与其体内增殖能力的降低相一致。pfs突变株的这些表型是LuxS/AI-2独立的,尽管pfs在AI-2生产中起重要作用。我们的数据表明Pfs是一个潜在的抗感染治疗的新靶点。(C)2013 Elsevier GmbH. All rights reserved.
Staphylococcus aureus is a major cause of infectious morbidity and mortality in both community and hospital settings. The bacterium continues to cause diverse invasive, life-threatening infections, such as pneumonia, endocarditis, and septicemia. Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) is predicted to be an important enzyme involved in methylation reactions, polyamine synthesis, vitamin synthesis, and quorum sensing pathways. For the first time, we demonstrate that Pfs is essential for the virulence of S. aureus. The pfs mutant strain, as compared to the isogenic wild type, displayed a decreased production of extracellular proteases, which was correlated with a dramatic decrease in the expression of the sspABC operon and a moderate decrease of aur expression. The mouse model of sepsis and subcutaneous abscesses indicated that the pfs mutant strain displayed highly impaired virulence compared to the isogenic wild type. The decreased virulence of the pfs mutant strain is in correspondence with its decreased proliferation in vivo, indicated with a real-time analysis in the transparent system of zebrafish embryos. These phenotypes of the pfs mutant strain are LuxS/AI-2 independent despite the essential role pfs plays in AI-2 production. Our data suggest that Pfs is a potential novel target for anti-infection therapy. (C) 2013 Elsevier GmbH. All rights reserved.