Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis
Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis
复制标题
DOI：
10.1046/j.1365-2958.1997.5151877.x
复制
发表时间：
1997-08-01
影响因子：
3.6
通讯作者：
Kroll, JS
中科院分区：
文献类型：
--
作者：
Farrant, JL;Sansone, A;Kroll, JS
铜/锌辅酶超氧化物歧化酶（[Cu,Zn]-SOD）存在于多种细菌的外周质中，但其生物学功能尚不清楚。本文报道了鼠伤寒沙门菌中编码[Cu，Zn]-SOD的sodC基因的克隆与鉴定。预测的蛋白质序列显示，与大肠杆菌SodC的同源性仅为58%，由此推测，其染色体位置及其与沙门氏菌中噬菌体基因SodC的直接邻近，可能是通过噬菌体介导的水平转移从未知供体获得的。鼠伤寒沙门氏菌的sodC突变体在富氧培养基中不受有氧生长的影响，但在体外对超氧化物的杀微生物作用表现出增强的敏感性。鼠伤寒沙门氏菌、霍乱沙门氏菌和都柏林沙门氏菌sodC突变体在小鼠口腔感染模型中表现出较低的致病性，并且在腹腔感染后肝脏和脾脏中的数量明显减少，这表明[Cu，Zn]-SOD在致病性中发挥作用，保护沙门氏菌免受氧自由基介导的宿主防御。然而，在体外实验中，与野生型相比，sodC突变体与猪胸膜、小鼠腹膜或J774巨噬细胞的相互作用没有明显差异，这可能反映了不同巨噬细胞株杀灭沙门氏菌的层次能力，最有效地击败了所提出的质周SOD的保护作用。
Copper/zinc-cofactored superoxide dismutase ([Cu,Zn]-SOD) has been found in the periplasm of many bacterial species but its biological function is unknown. Here we report the cloning and characterization of sodC, encoding [Cu,Zn]-SOD, from Salmonella typhimurium. The predicted protein sequence shows only 58% identity to Escherichia coli SodC, and from this its chromosomal location and its immediate proximity to a phage gene, sodC, in Salmonella is speculated to have been acquired by bacteriophage-mediated horizontal transfer from an unknown donor. A sodC mutant of S. typhimurium was unimpaired on aerobic growth in rich medium but showed enhanced sensitivity in vitro to the microbicidal action of superoxide. S. typhimurium, S. choleraesuis and S. dublin sodC mutants showed reduced lethality in a mouse model of oral infection and persisted in significantly lower numbers in livers and spleens after intraperitoneal infection, suggesting that [Cu,Zn]-SOD plays a role in pathogenicity, protecting Salmonella against oxygen radical-mediated host defences. There was, however, no observable difference compared with wild type in the interaction of sodC mutants with porcine pleural, mouse peritoneal or J774 macrophages in vitro, perhaps reflecting the hierarchical capacity of different macrophage lines to kill Salmonella, the most efficient overwhelming the proposed protective effect of periplasmic SOD.