Mycobactin-mediated iron acquisition within macrophages
Mycobactin-mediated iron acquisition within macrophages
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DOI：
10.1038/nchembio717
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发表时间：
2005-08-01
影响因子：
14.8
通讯作者：
Groves, JT
中科院分区：
文献类型：
--
作者：
Luo, MK;Fadeev, EA;Groves, JT
限制铁的利用率是防御细菌感染的重要策略(1-3)。结核分枝杆菌在巨噬细胞的吞噬体内存活；因此，结核分枝杆菌获取铁特别困难，因为吞噬体膜是其获取铁的额外屏障(4,5)。然而，人们对这种微生物在体内适应的铁转运和获取途径知之甚少(6)。细胞外铁源通常由亲水性铁载体动员(7,8)。在这里，我们描述了分枝杆菌素（分枝杆菌的亲脂性铁载体）可有效提取细胞内巨噬细胞铁的直接证据。不含金属的铁载体与巨噬细胞膜广泛结合，为铁螯合做好准备。值得注意的是，分枝杆菌素-金属复合物在巨噬细胞脂滴、用于脂质储存和分选的细胞内结构域中具有高选择性积累(9,10)。在我们的实验中，发现这些针对分枝杆菌素的脂滴与吞噬体直接接触，准备好铁的输送。这种先前未描述的铁获取途径的存在表明，分枝杆菌在感染期间利用内源性巨噬细胞机制进行铁动员和脂质分选来获取铁。该途径可能代表控制分枝杆菌感染的新目标。
Restricting the availability of iron is an important strategy for defense against bacterial infection(1-3). Mycobacterium tuberculosis survives within the phagosomes of macrophages; consequently, iron acquisition is particularly difficult for M. tuberculosis, because the phagosomal membrane is an additional barrier for its iron access(4,5). However, little is known about the iron transport and acquisition pathways adapted by this microbe in vivo(6). Extracellular iron sources are usually mobilized by hydrophilic siderophores(7,8). Here, we describe direct evidence that mycobactins, the lipophilic siderophores of mycobacteria, efficiently extract intracellular macrophage iron. The metal-free siderophore is diffusely associated with the macrophage membrane, ready for iron chelation. Notably, the mycobactin-metal complex accumulates with high selectivity in macrophage lipid droplets, intracellular domains for lipid storage and sorting(9,10). In our experiments, these mycobactin-targeted lipid droplets were found in direct contact with phagosomes, poised for iron delivery. The existence of this previously undescribed iron acquisition pathway indicates that mycobacteria have taken advantage of endogenous macrophage mechanisms for iron mobilization and lipid sorting for iron acquisition during infection. The pathway could represent a new target for the control of mycobacterial infection.