MdaB and NfrA, Two Novel Reductases Important in the Survival and Persistence of the Major Enteropathogen Campylobacter jejuni.
MdaB and NfrA, Two Novel Reductases Important in the Survival and Persistence of the Major Enteropathogen Campylobacter jejuni.
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MdaB和NfrA，两种对主要肠道病原体空肠弯曲菌的存活和持久性很重要的新还原酶。
DOI：
10.1128/jb.00421-21
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发表时间：
2022-01-18
影响因子：
3.2
通讯作者：
Wren BW
中科院分区：
文献类型：
--
作者：
Nasher F;Taylor AJ;Elmi A;Lehri B;Ijaz UZ;Baker D;Goram R;Lynham S;Singh D;Stabler R;Kelly DJ;Gundogdu O;Wren BW
旁系同源物RrpA和RrpB是DNA结合蛋白马尔R家族的成员，对全球细菌性食源性病原体空肠弯曲菌在氧化还原应激下的存活至关重要。我们报告说，RrpA是一个积极的调节mdaB，编码一个黄素依赖性醌还原酶，有助于保护从氧化还原应激介导的结构不同的醌类，而RrpB负调节cj 1555 c（nfrA的NADPH-黄素还原酶A），编码黄素还原酶的表达。NfrA以比其衍生物更大的速率还原核黄素，表明外源游离黄素是天然底物。MdaB和NfrA都喜欢NADPH作为电子供体。半胱氨酸取代和翻译后修饰分析表明，RrpA和RrpB采用半胱氨酸为基础的氧化还原开关。全基因组序列分析显示，mdaB经常在弯曲杆菌和相关的螺杆菌属中发现，而nfrA在C.空肠菌株。醌和黄素是由多种细胞类型分泌的氧化还原循环剂，其可以通过单电子反应形成破坏性的超氧化物。我们提出了一个模型的压力适应MdaB和NfrA促进双电子还原机制毒性较小的氢醌，从而帮助生存和持久性的这一主要病原体。细胞氧化还原电位的变化导致细胞内代谢物和酶的氧化状态改变;因此，细胞做出有利于生长和存活的调整。我们在这里提出的工作回答了多年来对神秘的微需氧细菌空肠弯曲菌的调查中仍然难以捉摸的许多问题中的一些。我们采用分子方法来了解的调节机制和功能分析，以揭示两个新的醌和黄素还原酶的作用，都作为细胞氧化还原活性分子的主要池。这项工作扩展了我们对细菌氧化还原传感机制和止血意义的认识。
The paralogues RrpA and RrpB, which are members of the MarR family of DNA binding proteins, are important for the survival of the global bacterial foodborne pathogen Campylobacter jejuni under redox stress. We report that RrpA is a positive regulator of mdaB, encoding a flavin-dependent quinone reductase that contributes to the protection from redox stress mediated by structurally diverse quinones, while RrpB negatively regulates the expression of cj1555c (renamed nfrA for NADPH-flavin reductase A), encoding a flavin reductase. NfrA reduces riboflavin at a greater rate than its derivatives, suggesting that exogenous free flavins are the natural substrate. MdaB and NfrA both prefer NADPH as an electron donor. Cysteine substitution and posttranslational modification analyses indicated that RrpA and RrpB employ a cysteine-based redox switch. Complete genome sequence analyses revealed that mdaB is frequently found in Campylobacter and related Helicobacter spp., while nfrA is predominant in C. jejuni strains. Quinones and flavins are redox cycling agents secreted by a wide range of cell types that can form damaging superoxide by one-electron reactions. We propose a model for stress adaptation where MdaB and NfrA facilitate a two-electron reduction mechanism to the less toxic hydroquinones, thus aiding survival and persistence of this major pathogen. IMPORTANCE Changes in cellular redox potential result in alteration in the oxidation state of intracellular metabolites and enzymes; consequently, cells make adjustments that favor growth and survival. The work we present here answers some of the many questions that have remained elusive over the years of investigation into the enigmatic microaerophile bacterium Campylobacter jejuni. We employed molecular approaches to understand the regulation mechanisms and functional analyses to reveal the roles of two novel quinone and flavin reductases; both serve as major pools of cellular redox-active molecules. This work extends our knowledge on bacterial redox sensing mechanisms and the significance of hemostasis.