Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase
Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase
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DOI：
10.1073/pnas.94.25.13997
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Fang, FC
中科院分区：
文献类型：
--
作者：
DeGroote, MA;Ochsner, UA;Fang, FC
超氧化物歧化酶(SOD)催化超氧阴离子自由基转化为过氧化氢。细菌铜，锌-超氧化物歧化酶的周质定位表明，该酶在防御细胞外吞噬细胞衍生的活性氧物种中起到了作用。对鼠伤寒沙门氏菌SODC基因编码铜、锌-超氧化物歧化酶基因两侧的序列分析表明，该基因与噬菌体蛋白有显著的同源性，反映了该决定簇在病原菌之间可能通过噬菌体介导的水平基因转移。缺乏铜，锌-超氧化物歧化酶的沙门氏菌降低了巨噬细胞的存活率，并减弱了小鼠的毒力，这可以通过取消吞噬细胞呼吸爆发或诱导型一氧化氮合酶来恢复。此外，SODC突变体对超氧化物和一氧化氮的组合非常敏感。这些观察表明，SOD通过转移超氧化物歧化和限制过氧亚硝酸盐的形成来保护周质或内膜靶标，并证明了呼吸爆发和一氧化氮合酶在体内协同杀灭微生物病原体的能力。
Superoxide dismutase (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide. Periplasmic localization of bacterial Cu,Zn-SOD has suggested a role of this enzyme in defense against extracellular phagocyte-derived reactive oxygen species. Sequence analysis of regions flanking the Salmonella typhimurium sodC gene encoding Cu,Zn-SOD demonstrates significant homology toh phage proteins, reflecting possible bacteriophage-mediated horizontal gene transfer of this determinant among pathogenic bacteria. Salmonella deficient in Cu,Zn-SOD has reduced survival in macrophages and attenuated virulence in mice, which can be restored by abrogation of either the phagocyte respiratory burst or inducible nitric oxide synthase. Moreover, a sodC mutant is extremely susceptible to the combination of superoxide and nitric oxide. These observations suggest that SOD protects periplasmic or inner membrane targets by diverting superoxide and limiting peroxynitrite formation, and they demonstrate the ability of the respiratory burst and nitric oxide synthase to synergistically kill microbial pathogens in vivo.