Hal Is a Bacillus anthracis Heme Acquisition Protein
Hal Is a Bacillus anthracis Heme Acquisition Protein
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DOI：
10.1128/jb.00685-12
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发表时间：
2012-10-01
影响因子：
3.2
通讯作者：
Maresso, Anthony W.
中科院分区：
文献类型：
--
作者：
Balderas, Miriam A.;Nobles, Christopher L.;Maresso, Anthony W.
金属铁是细菌在感染期间的限制性营养素。炭疽杆菌是炭疽病的病原体，也是生物恐怖主义的潜在武器，它在哺乳动物宿主中生长迅速，这表明它在感染过程中有效地获得铁。最近的研究揭示了血红素（isd）和铁载体介导的（asb）铁转运途径在这种病原体。尽管asB基因的缺失导致毒力降低，但isd的三种表面组分的缺失没有影响，因此留下了B中有哪些额外因子的问题。炭疽菌负责从哺乳动物最丰富的铁源血红素中摄取铁。在这里，我们描述了bas0520的第一个功能特性，最近在炭疽病的进展有牵连的基因。bas0520编码一个近铁转运蛋白（NEAT）结构域和几个富含亮氨酸的重复序列。NEAT结构域结合血红素，尽管缺乏血红素蛋白NEAT超家族共有的稳定酪氨酸。NEAT结构域也结合血红蛋白，并且可以从溶液中的血红蛋白获得血红素。最后，bas0520的缺失导致杆菌不能有效地生长在血红素或血红蛋白作为铁源，并产生了最显着的表型相对于其他推定的血红素摄取系统，结果表明，这种蛋白质在复制B中起着重要作用。炭疽病在血行环境中。因此，我们将Hal（血红素获取富含亮氨酸重复蛋白）命名为BAS 0520。这些研究推进了我们对这种危险病原体血红素获取的理解，并证明了确定这种新型蛋白质用于疫苗或抑制剂开发的机制功能的努力是合理的。
The metal iron is a limiting nutrient for bacteria during infection. Bacillus anthracis, the causative agent of anthrax and a potential weapon of bioterrorism, grows rapidly in mammalian hosts, which suggests that it efficiently attains iron during infection. Recent studies have uncovered both heme (isd) and siderophore-mediated (asb) iron transport pathways in this pathogen. Whereas deletion of the asb genes results in reduced virulence, the loss of three surface components from isd had no effect, thereby leaving open the question of what additional factors in B. anthracis are responsible for iron uptake from the most abundant iron source for mammals, heme. Here, we describe the first functional characterization of bas0520, a gene recently implicated in anthrax disease progression. bas0520 encodes a single near-iron transporter (NEAT) domain and several leucine-rich repeats. The NEAT domain binds heme, despite lacking a stabilizing tyrosine common to the NEAT superfamily of hemoproteins. The NEAT domain also binds hemoglobin and can acquire heme from hemoglobin in solution. Finally, deletion of bas0520 resulted in bacilli unable to grow efficiently on heme or hemoglobin as an iron source and yielded the most significant phenotype relative to that for other putative heme uptake systems, a result that suggests that this protein plays a prominent role in the replication of B. anthracis in hematogenous environments. Thus, we have assigned the name of Hal (heme-acquisition leucine-rich repeat protein) to BAS0520. These studies advance our understanding of heme acquisition by this dangerous pathogen and justify efforts to determine the mechanistic function of this novel protein for vaccine or inhibitor development.