SodA is a major metabolic antioxidant in Brucella abortus 2308 that plays a significant, but limited, role in the virulence of this strain in the mouse model.

SodA is a major metabolic antioxidant in Brucella abortus 2308 that plays a significant, but limited, role in the virulence of this strain in the mouse model.
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SodA 是流产布鲁氏菌 2308 中的一种主要代谢抗氧化剂,在小鼠模型中该菌株的毒力中发挥着重要但有限的作用。

DOI:
10.1099/mic.0.059584-0
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发表时间:
2012
期刊:
Microbiology (Reading, England)
影响因子:
--
通讯作者:
Roop,RMartin
Roop,RMartin
中科院分区:
--
文献类型:
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作者:
Martin,DanielW;Baumgartner,JohnE;Gee,JasonM;Anderson,EricS;Roop,RMartin

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流产布鲁氏菌2308基因组序列中命名为BAB1_0591的基因编码锰辅因子超氧化物歧化酶SodA。从B.命名为JB12的abortus2308显示出小菌落表型,体外对内源性超氧化物发生剂、过氧化氢和暴露于酸性pH的敏感性增加,并且当在丰富和基本培养基中培养时生长滞后,这可以通过向生长培养基中添加所有20种氨基酸来挽救。abortusJB12在培养的鼠巨噬细胞和实验感染的小鼠中都表现出显著的减毒,但这种减毒仅限于感染的早期阶段。向感染的巨噬细胞中加入NADPH氧化酶抑制剂夹竹桃苷不能减轻JB12所表现出的衰减,这表明B.牛流产杆菌sodA突变体不是通过宿主吞噬细胞的氧化爆发产生的对外源性超氧化物的敏感性增加。然而,B.牛种布氏杆菌对酸的突变使其对巨噬细胞中含布鲁氏杆菌空泡发育早期所遇到的低pH杀死的抗性低于亲本菌株。这些实验结果支持了SodA在布鲁氏菌中作为主要细胞质抗氧化剂的作用。尽管这种酶对B.在巨噬细胞和小鼠中感染的早期阶段,一旦布鲁氏菌已经建立感染,SodA似乎被抑制。
The gene designated BAB1_0591 in theBrucella abortus2308 genome sequence encodes the manganese-cofactored superoxide dismutase SodA. An isogenicsodAmutant derived fromB. abortus2308, designated JB12, displays a small colony phenotype, increased sensitivityin vitroto endogenous superoxide generators, hydrogen peroxide and exposure to acidic pH, and a lag in growth when cultured in rich and minimal media that can be rescued by the addition of all 20 amino acids to the growth medium.B. abortusJB12 exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, but this attenuation is limited to the early stages of infection. Addition of the NADPH oxidase inhibitor apocynin to infected macrophages does not alleviate the attenuation exhibited by JB12, suggesting that the basis for the attenuation of theB. abortus sodAmutant is not an increased sensitivity to exogenous superoxide generated through the oxidative burst of host phagocytes. It is possible, however, that the increased sensitivity of theB. abortus sodAmutant to acid makes it less resistant than the parental strain to killing by the low pH encountered during the early stages of the development of the brucella-containing vacuoles in macrophages. These experimental findings support the proposed role for SodA as a major cytoplasmic antioxidant in brucella. Although this enzyme provides a clear benefit toB. abortus2308 during the early stages of infection in macrophages and mice, SodA appears to be dispensable once the brucellae have established an infection.