Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin.
Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin.
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炭疽芽孢杆菌分泌从血红蛋白中介导血红素的蛋白质。
DOI：
10.1371/journal.ppat.1000132
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发表时间：
2008-08-22
期刊：
影响因子：
6.7
通讯作者：
Schneewind, Olaf
中科院分区：
文献类型：
--
作者：
Maresso, Anthony W.;Garufi, Gabriella;Schneewind, Olaf
铁的获取是几乎所有细菌病原体复制所必需的；然而，脊椎动物宿主的铁大多被血红素隔离，并与红细胞内的血红蛋白结合。在炭疽芽孢杆菌中，炭疽的孢子形成剂，从血红蛋白中清除铁的机制尚不清楚。我们在这里报道，炭疽杆菌分泌IsdX1和IsdX2，两种NEAT结构域蛋白，从血红蛋白中去除血红素，从而为细菌生长回收铁。与其他依靠细胞壁固定的Isd蛋白清除血红素的革兰氏阳性细菌不同，炭疽芽胞杆菌似乎也在细胞外环境和细菌包膜中进化出了NEAT结构域蛋白，以提供血红素的传递。铁是几乎所有生物体所必需的营养物质。细菌病原体必须获得铁才能在哺乳动物宿主体内生长。然而，宿主限制了游离铁的可用性，从而提供了一种有效的防御感染的策略。作为回应，细菌进化出了巧妙的方法来破坏宿主对铁的隔离。在这项工作中，我们报道了炭疽病的病原体，炭疽芽孢杆菌，产生两种蛋白质（IsdX1和IsdX2），它们的作用是获得铁与血红素的复合物，血红素是宿主血红蛋白（如血红蛋白）的辅助因子。这种活性依赖于在许多革兰氏阳性细菌病原体中发现的保守蛋白结构域，是炭疽芽孢杆菌在低铁环境中生长所必需的。我们的研究结果对细菌病原体破坏宿主防御的机制有了更深入的了解，并为开发旨在阻断这些策略的抗感染药物提供了一条途径。
Acquisition of iron is necessary for the replication of nearly all bacterial pathogens; however, iron of vertebrate hosts is mostly sequestered by heme and bound to hemoglobin within red blood cells. In Bacillus anthracis, the spore-forming agent of anthrax, the mechanisms of iron scavenging from hemoglobin are unknown. We report here that B. anthracis secretes IsdX1 and IsdX2, two NEAT domain proteins, to remove heme from hemoglobin, thereby retrieving iron for bacterial growth. Unlike other Gram-positive bacteria, which rely on cell wall anchored Isd proteins for heme scavenging, B. anthracis seems to have also evolved NEAT domain proteins in the extracellular milieu and in the bacterial envelope to provide for the passage of heme. Iron is an essential nutrient used by almost all organisms. Bacterial pathogens must acquire iron in order to grow inside mammalian hosts. The host, however, limits the availability of free iron, thereby providing an effective defense strategy against infection. In response, bacteria have evolved clever ways to subvert host sequestration of iron. In this work, we report that the causative agent of anthrax disease, Bacillus anthracis, produces two proteins (IsdX1 and IsdX2), which act to acquire iron complexed to heme, a co-factor of host hemoproteins such as hemoglobin. This activity is dependent on a conserved protein domain found in many Gram-positive bacterial pathogens and is necessary for growth of B. anthracis in low-iron environments. Our results yield a greater understanding of the mechanisms used by bacterial pathogens to subvert host defenses and provide an avenue for the development of antiinfectives that aim to block these strategies.
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