Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis.

Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis.
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DOI:
10.1096/fj.08-128330
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发表时间:
2010-01
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
Read RC
Read RC
中科院分区:
其他
文献类型:
--
作者:
Laver JR;Stevanin TM;Messenger SL;Lunn AD;Lee ME;Moir JW;Poole RK;Read RC

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S亚硝化是多种一氧化氮依赖的生物过程的重要介质,包括真核细胞事件,如巨噬细胞凋亡和促炎信号转导。许多病原菌没有解毒机制,如脑膜炎奈瑟氏菌的一氧化氮合酶(NorB)、肠沙门氏菌和大肠杆菌的黄色素(HMP),这些机制有助于保护微生物免受细胞内环境中的亚硝酸盐应激。在这项研究中,我们证明脑膜炎球菌NorB的表达增加了低分子S亚硝硫醇(SNO)的体外分解速度。为了确定这种影响是否发生在细菌感染的细胞中,我们通过内毒素和γ-干扰素激活小鼠巨噬细胞诱导一氧化氮的形成,并观察到在与脑膜炎奈瑟氏菌、肠杆菌或大肠杆菌共同孵育时,一氧化氮的丰度降低。在每种情况下,这种效应都被证明依赖于细菌的NO解毒基因,这些基因通过去除NO来防止SNO的形成。这可能代表了细菌对宿主细胞损伤的一种新机制。-Laver,J.R.,Stevanin,T.M.,Messenger,S.L.,Dehn Lumn,A.,Lee,M.E.,Moir,J.W.B.,Poole,R.K.,Read,R.C.细菌一氧化氮解毒防止宿主细胞S-亚硝硫醇的形成:一种细菌致病的新机制。
S-nitrosylation is an important mediator of multiple nitric oxide-dependent biological processes, including eukaryotic cellular events such as macrophage apoptosis and proinflammatory signaling. Many pathogenic bacteria possess NO detoxification mechanisms, such as the nitric oxide reductase (NorB) of Neisseria meningitidis and the flavohemoglobins (Hmp) of Salmonella enterica and Escherichia coli, which serve to protect the microorganism from nitrosative stress within the intracellular environment. In this study, we demonstrate that expression of meningococcal NorB increases the rate at which low-molecular-weight S-nitrosothiol (SNO) decomposes in vitro. To determine whether this effect occurs in cells during infection by bacteria, we induced SNO formation in murine macrophages by activation with lipopolysaccharide and γ-interferon and observed a reduced abundance of SNO during coincubation with N. meningitidis, S. enterica, or E. coli. In each case, this effect was shown to be dependent on bacterial NO detoxification genes, which act to prevent SNO formation through the removal of NO. This may represent a novel mechanism of host cell injury by bacteria.—Laver, J. R., Stevanin, T. M., Messenger, S. L., Dehn Lunn, A., Lee, M. E., Moir, J. W. B., Poole, R. K., Read, R. C. Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis.
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