Nitrosative damage to free and zinc-bound cysteine thiols underlies nitric oxide toxicity in wild-type Borrelia burgdorferi.
Nitrosative damage to free and zinc-bound cysteine thiols underlies nitric oxide toxicity in wild-type Borrelia burgdorferi.
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DOI：
10.1111/j.1365-2958.2011.07691.x
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发表时间：
2011-07
影响因子：
3.6
通讯作者：
Gherardini FC
中科院分区：
文献类型：
--
作者：
Bourret TJ;Boylan JA;Lawrence KA;Gherardini FC
伯氏疏螺旋体在其整个感染周期中遇到潜在有害的活性氮物质（RNS）。在这项研究中，二乙胺NONOate（DEA/NO）被用来表征RNS对B的致死作用。burgdorferi。RNS在广谱微生物病原体中产生各种DNA损伤;然而，从未处理和DEA/NO处理的B分离的DNA中，DNA脱氨基产物脱氧肌苷的水平和脱嘌呤/脱嘧啶（AP）位点的数量是相同的。伯氏细胞与野生型对照相比，用DEA/NO处理的核苷酸切除修复（NER）途径基因uvrC或uvrB突变的菌株具有显著更高的自发突变频率，DNA中AP位点的数量增加，存活率降低。B中的多不饱和脂肪酸。对活性氧（ROS）过氧化反应敏感的伯氏细胞膜对RNS介导的脂质过氧化反应不敏感。然而，治疗B。用DEA/NO处理burgdorferi细胞导致几种蛋白质的亚硝化损伤，包括锌依赖性糖酵解酶果糖-1，6-二磷酸醛缩酶（BB 0445）、疏螺旋体氧化应激调节剂（BosR）和嗜热菌活化蛋白（NapA）。总的来说，这些数据表明，亚硝化损伤蛋白窝藏自由或锌结合的半胱氨酸硫醇，而不是DNA或膜脂质的RNS毒性野生型B。burgdorferi。
Borrelia burgdorferi encounters potentially harmful reactive nitrogen species (RNS) throughout its infective cycle. In this study, diethylamine NONOate (DEA/NO) was used to characterize the lethal effects of RNS on B. burgdorferi. RNS produce a variety of DNA lesions in a broad spectrum of microbial pathogens; however, levels of the DNA deamination product, deoxyinosine, and the numbers of apurinic/apyrimidinic (AP) sites were identical in DNA isolated from untreated and DEA/NO-treated B. burgdorferi cells. Strains with mutations in the nucleotide excision repair (NER) pathway genes uvrC or uvrB treated with DEA/NO had significantly higher spontaneous mutation frequencies, increased numbers of AP sites in DNA and reduced survival compared with wild-type controls. Polyunsaturated fatty acids in B. burgdorferi cell membranes, which are susceptible to peroxidation by reactive oxygen species (ROS), were not sensitive to RNS-mediated lipid peroxidation. However, treatment of B. burgdorferi cells with DEA/NO resulted in nitrosative damage to several proteins, including the zinc-dependent glycolytic enzyme fructose-1,6-bisphosphate aldolase (BB0445), the Borrelia oxidative stress regulator (BosR) and neutrophil-activating protein (NapA). Collectively, these data suggested that nitrosative damage to proteins harbouring free or zinc-bound cysteine thiols, rather than DNA or membrane lipids underlies RNS toxicity in wild-type B. burgdorferi.
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影响因子：
2.1
作者：
Bhattacharya, ST;Bayakly, N;Coons, LB
通讯作者：
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影响因子：
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作者：
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