Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall.
Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall.
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结核分枝杆菌的外塞蛋白从人体结合蛋白中去除铁，并将铁捐赠给结核分枝杆菌细胞壁中的霉菌素。
DOI：
10.1084/jem.183.4.1527
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发表时间：
1996-04-01
影响因子：
15.3
通讯作者：
Horwitz, MA
中科院分区：
文献类型：
--
作者：
Gobin, J;Horwitz, MA
为了在宿主中繁殖并引起疾病，结核分枝杆菌必须在复制位点从细胞外环境获得铁。为了做到这一点，细菌释放出高亲和力的铁结合铁载体，称为外螯素。在以前的研究中，我们已经描述了外螯素家族分子的纯化和表征。这些分子与位于M细胞壁中的另一种高亲和力铁结合分子共享共同的核心结构。结核病：分枝杆菌素。水溶性外螯素在极性上彼此不同，并且与水不溶性分枝杆菌素不同，这主要取决于烷基侧链的长度和修饰。在这项研究中，我们已经调查了纯化的exochelins的能力，以消除铁从主机高亲和力的铁结合分子，并将铁转移到分枝杆菌素。纯化的去铁-外螯铁蛋白快速地从人转铁蛋白和人乳铁蛋白中去除铁，无论它是95%还是40%的铁饱和，其在人血清中的近似百分比饱和。去铁外螯素也从铁储存蛋白铁蛋白中去除铁，但速度较慢。纯化的铁外螯素（而不是铁转铁蛋白）将铁转移到活细菌细胞壁中的去铁分枝杆菌素。为了探讨铁离子从外螯素向分枝杆菌素的转移受其极性影响的可能性，我们研究了极性对外螯素铁亲和力的影响。不同极性的外螯素彼此平等地交换铁。本研究支持外螯素为M.通过从宿主铁结合蛋白中去除该元素并将其转移到细菌细胞壁中的去铁分枝杆菌素来治疗结核病。铁-外螯素而不是铁转铁蛋白将铁转移到细胞壁中的分枝杆菌素的发现强调了外螯素在铁获取中的重要性。这项研究还表明，可变的烷基侧链上的核心结构的exochelins和mycobactins，其极性的主要决定因素，对它们的铁亲和力几乎没有影响。
To multiply and cause disease in the host, Mycobacterium tuberculosis must acquire iron from the extracellular environment at sites of replication. To do so, the bacterium releases high-affinity iron- binding siderophores called exochelins. In previous studies, we have described the purification and characterization of the exochelin family of molecules. These molecules share a common core structure with another type of high-affinity iron-binding molecule located in the cell wall of M. tuberculosis: the mycobactins. The water-soluble exochelins differ from each other and from water insoluble mycobactins in polarity, which is dependent primarily upon the length and modifications of an alkyl side chain. In this study, we have investigated the capacity of purified exochelins to remove iron from host high-affinity iron-binding molecules, and to transfer iron to mycobactins. Purified desferri-exochelins rapidly removed iron from human transferrin, whether it was 95 or 40% iron saturated, its approximate percent saturation in human serum, and from human lactoferrin. Desferri-exochelins also removed iron, but at a slower rate, from the iron storage protein ferritin. Purified ferri- exochelins, but not iron transferrin, transferred iron to desferri- mycobactins in the cell wall of live bacteria. To explore the possibility that the transfer iron from exochelins to mycobactins was influenced by their polarity, we investigated the influence of polarity on the iron affinity of exochelins. Exochelins of different polarity exchanged iron equally with each other. This study supports the concept that exochelins acquire iron for M. tuberculosis by removing this element from host iron-binding proteins and transferring it to desferri- mycobactins in the cell wall of the bacterium. The finding that ferri- exochelins but not iron transferrin transfer iron to mycobactins in the cell wall underscores the importance of exochelins in iron acquisition. This study also shows that the variable alkyl side chain on the core structure of exochelins and mycobactins, the principal determinant of their polarity, has little or no influence on their iron affinity.
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影响因子：
15.9
作者：
BYRD, TF;HORWITZ, MA
通讯作者：
HORWITZ, MA
DOI：
10.1073/pnas.92.11.5189
发表时间：
1995-05-23
影响因子：
11.1
作者：
GOBIN, J;MOORE, CH;HORWITZ, MA
通讯作者：
HORWITZ, MA
影响因子：
3.1
作者：
CROWLE, AJ;DAHL, R;MAY, MH
通讯作者：
MAY, MH
影响因子：
15.9
作者：
BYRD, TF;HORWITZ, MA
通讯作者：
HORWITZ, MA
影响因子：
15.3
作者：
Clemens, Daniel L.;Horwitz, Marcus A.
通讯作者：
Horwitz, Marcus A.