Host Nitric Oxide Disrupts Microbial Cell-to-Cell Communication to Inhibit Staphylococcal Virulence.
Host Nitric Oxide Disrupts Microbial Cell-to-Cell Communication to Inhibit Staphylococcal Virulence.
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DOI：
10.1016/j.chom.2018.04.001
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发表时间：
2018-05-09
影响因子：
30.3
通讯作者：
Fang FC
中科院分区：
文献类型：
--
作者：
Urbano R;Karlinsey JE;Libby SJ;Doulias PT;Ischiropoulos H;Warheit-Niemi HI;Liggitt DH;Horswill AR;Fang FC
金黄色葡萄球菌（Staphylococcus aureus）是一种细菌，可以无症状地在宿主体内定植，但也会引起侵入性感染。群体感应调节S.金黄色葡萄球菌毒力和从细菌到致病生物体的转变。然而，很少有人知道宿主先天免疫如何影响细菌间的通信。我们表明，一氧化氮抑制葡萄球菌的毒力，针对Agr群体感应系统。一氧化氮介导的抑制作用通过直接修饰AgrA转录因子的半胱氨酸残基C55、C123和C199而发生。半胱氨酸修饰降低了AgrA启动子的占用率以及agr操纵子和群体感应激活毒素基因的转录。在葡萄球菌肺炎模型中，缺乏诱导型一氧化氮合酶的小鼠发展为更严重的疾病，死亡率和促炎细胞因子反应增加。此外，葡萄球菌α-毒素的产生在一氧化氮或一氧化氮敏感的AgrA半胱氨酸残基不存在的情况下增加。我们的研究结果证明了一氧化氮在先天免疫中的抗毒性机制。群体感应调节葡萄球菌的毒力并介导S.金黄色葡萄球菌从细菌生物体转化为病原体。Urbano等人证明，先天免疫分子一氧化氮可以直接靶向群体感应调节剂AgrA，以抑制毒素产生并保护宿主免受葡萄球菌感染。
Staphylococcus aureus is a commensal bacterium that can asymptomatically colonize its host but also causes invasive infections. Quorum sensing regulates S. aureus virulence and the transition from a commensal to a pathogenic organism. However, little is known about how host innate immunity affects interbacterial communication. We show that nitric oxide suppresses staphylococcal virulence by targeting the Agr quorum sensing system. Nitric oxide-mediated inhibition occurs through direct modification of cysteine residues C55, C123, and C199 of the AgrA transcription factor. Cysteine modification decreases AgrA promoter occupancy as well as transcription of the agr operon and quorum sensing-activated toxin genes. In a staphylococcal pneumonia model, mice lacking inducible nitric oxide synthase develop more severe disease with heightened mortality and pro-inflammatory cytokine responses. Additionally, staphylococcal α-toxin production increases in the absence of nitric oxide or nitric oxide-sensitive AgrA cysteine residues. Our findings demonstrate an anti-virulence mechanism for nitric oxide in innate immunity. Quorum sensing regulates staphylococcal virulence and mediates the transition of S. aureus from a commensal organism to a pathogen. Urbano et al. demonstrate that the innate immunity molecule nitric oxide can directly target the quorum sensing regulator AgrA to inhibit toxin production and protect the host against staphylococcal infection.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
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作者：
Bang, Iel-Soo;Liu, Limin;Fang, Ferric C.
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影响因子：
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作者：
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Steinmetz, Ivo
DOI：
10.1073/pnas.1008036107
发表时间：
2010-09-28
影响因子：
11.1
作者：
Doulias, Paschalis-Thomas;Greene, Jennifer L.;Ischiropoulos, Harry
通讯作者：
Ischiropoulos, Harry
影响因子：
6.7
作者：
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通讯作者：
Gresham HD