An Atypical Riboflavin Pathway Is Essential for Brucella abortus Virulence
An Atypical Riboflavin Pathway Is Essential for Brucella abortus Virulence
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DOI：
10.1371/journal.pone.0009435
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发表时间：
2010-02-25
期刊：
影响因子：
3.7
通讯作者：
Alberto Goldbaum, Fernando
中科院分区：
文献类型：
--
作者：
Ruy Bonomi, Hernan;Ines Marchesini, Maria;Alberto Goldbaum, Fernando
布鲁氏菌病是一种世界性的人畜共患病，影响牲畜和人类，由密切相关的布鲁氏菌属引起，其适应于多种哺乳动物细胞内的细胞内生活。布鲁氏菌可以被认为是一种隐秘的病原体，感染专业和非专业的吞噬细胞。在这些细胞中，布鲁氏菌存活在复制生态位中，其特征在于具有非常低的氧张力并且被剥夺营养物如氨基酸和维生素。在这些维生素中，我们重点关注核黄素（维生素B2）。黄素代谢与细菌的毒力几乎没有关系。我们最近描述了布鲁氏菌和其他根瘤菌具有非典型的核黄素代谢途径。在目前的工作中，我们分析了黄素代谢对布鲁氏菌毒力的作用。产生了两种乌马肼脱氢酶（LS）同工酶RibH1和RibH2的突变体和双RibH突变体。在细胞和小鼠中测试这些突变体和不同补充菌株的活力和毒力。以这种方式，我们已经建立了至少一个LS必须存在于B。流产存活，并且RibH2而不是RibH1由于其体内LS活性对于细胞内存活是必需的。总之，我们表明核黄素的生物合成对于布鲁氏菌在细胞内或小鼠中的存活是必不可少的。这些结果突出了黄素生物合成途径酶作为布鲁氏菌病化疗靶点的潜在用途。
Brucellosis is a worldwide zoonosis that affects livestock and humans and is caused by closely related Brucella spp., which are adapted to intracellular life within cells of a large variety of mammals. Brucella can be considered a furtive pathogen that infects professional and non-professional phagocytes. In these cells Brucella survives in a replicative niche, which is characterized for having a very low oxygen tension and being deprived from nutrients such as amino acids and vitamins. Among these vitamins, we have focused on riboflavin (vitamin B2). Flavin metabolism has been barely implicated in bacterial virulence. We have recently described that Brucella and other Rhizobiales bear an atypical riboflavin metabolic pathway. In the present work we analyze the role of the flavin metabolism on Brucella virulence. Mutants on the two lumazine synthases (LS) isoenzymes RibH1 and RibH2 and a double RibH mutant were generated. These mutants and different complemented strains were tested for viability and virulence in cells and in mice. In this fashion we have established that at least one LS must be present for B. abortus survival and that RibH2 and not RibH1 is essential for intracellular survival due to its LS activity in vivo. In summary, we show that riboflavin biosynthesis is essential for Brucella survival inside cells or in mice. These results highlight the potential use of flavin biosynthetic pathway enzymes as targets for the chemotherapy of brucellosis.