Periplasmic Superoxide Dismutase in Meningococcal Pathogenicity

Periplasmic Superoxide Dismutase in Meningococcal Pathogenicity
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周质超氧化物歧化酶在脑膜炎球菌致病性中的作用

DOI:
10.1128/iai.66.1.213-217.1998
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发表时间:
1998
影响因子:
3.1
通讯作者:
J. S. Kroll
J. S. Kroll
中科院分区:
医学2区
文献类型:
--
作者:
Kathryn E. Wilks;Kate L. R. Dunn;J. Farrant;Karen M. Reddin;A. Gorringe;P. R. Langford;J. S. Kroll

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脑膜炎双球菌SODC编码胞质铜锌共因子超氧化物歧化酶(CuZSOD),它催化超氧阴离子转化为过氧化氢,阻止一系列反应导致有毒的羟基自由基的产生。根据其周质位置推测,铜锌超氧化物歧化酶是从细菌细胞外获得底物的,推测其在保护脑膜炎球菌免受宿主防御产生的杀菌氧自由基的作用方面发挥了作用。通过等位基因交换构建了SODC突变体,并利用该突变体研究了铜锌超氧化物歧化酶在致病中的作用。野生型和突变型脑膜炎双球菌在好氧液体培养中的生长速度相似,存活时间相同。该突变体对百草枯的敏感性没有增加,百草枯在细胞质中产生超氧化物,但对黄嘌呤/黄嘌呤氧化酶系统在溶液中产生的超氧化物的毒性大约敏感1000倍。这些数据支持脑膜炎球菌铜、锌超氧化物歧化酶对外源性超氧化物歧化的保护作用。在将其转化为致病作用的实验中,野生型和突变型生物被用于小鼠腹膜内感染模型。SODC突变体的毒力要低得多。我们的结论是,脑膜炎奈瑟氏菌胞质中的铜锌超氧化物歧化酶可能通过降低有毒氧宿主防御系统的有效性而导致其毒力增加。
ABSTRACT Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals. From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense. A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture. The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system. These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide. In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model. The sodC mutant was significantly less virulent. We conclude that periplasmic Cu,Zn SOD contributes to the virulence ofNeisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.
DOI: 10.1016/0022-2836(82)90174-7
发表时间: 1982-01-01
影响因子: 5.6
作者:
TAINER, JA;GETZOFF, ED;RICHARDSON, DC
通讯作者: RICHARDSON, DC
DOI: 10.1016/s0021-9258(18)47248-1
发表时间: 1994-10
期刊: The Journal of biological chemistry
影响因子: --
作者:
Ludmil T. BenovS;Irwin Fridovichg
通讯作者: Ludmil T. BenovS;Irwin Fridovichg
人铜锌超氧化物歧化酶可补充超氧化物歧化酶缺陷的大肠杆菌突变体。
DOI: --
发表时间: 1987
期刊: The Journal of biological chemistry
影响因子: --
作者:
Natvig,DO;Imlay,K;Touati,D;Hallewell,RA
通讯作者: Hallewell,RA