Avoidance of iron toxicity through regulation of bacterial iron transport.
Avoidance of iron toxicity through regulation of bacterial iron transport.
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作者：
V. Braun
在好氧条件和pH 7下，三价铁是不溶的，并且需要Fe 3+与配体形成络合物以向细胞供应铁。细菌和真菌合成并分泌低分子量化合物，称为铁载体，结合Fe 3+。某些人类病原体从人转铁蛋白、乳铁蛋白、血红蛋白和血红素中摄取铁。铁载体通过高度特异性的转运系统主动转运到细菌细胞中。在革兰氏阴性细菌中，从宿主蛋白质释放的铁载体和铁被主动转运穿过外膜（OM）。细胞质膜（CM）的电化学电势为跨外膜的运输提供能量，这需要由蛋白质TonB、ExbB和ExbD组成的能量转换装置从CM到OM。跨CM的主动运输由ATP水解提供能量。转运在基因转录水平上受到调节。在革兰氏阴性细菌中，这是由Fur蛋白控制的，在大多数革兰氏阳性细菌中，由DtxR蛋白控制。当负载Fe 2+时，Fur和DtxR充当阻遏物。在细胞质中，铁通过还原为Fe 2+从铁载体释放，并且铁载体被灭活或分泌。细胞内的铁被构建到血红素和非血红素铁蛋白中，并且一小部分被并入细菌铁蛋白中，但是大部分铁以不明确的状态存在。铁过载导致铁毒性，主要是由于形成与各种生物分子强烈反应的羟基自由基，其中DNA损伤具有最有害的后果。
Under oxic conditions and at pH 7, ferric iron is insoluble, and complex formation of Fe3+ with ligands is required to supply cells with iron. Bacteria and fungi synthesize and secrete low-molecular-weight compounds, termed siderophores, that bind Fe3+. Certain human pathogens take up iron from human transferrin, lactoferrin, hemoglobin, and heme. The ferric siderophores are actively transported into bacterial cells by highly specific transport systems. In Gram-negative bacteria, the ferric siderophores and iron released from the host proteins are actively transported across the outer membrane (OM). The electrochemical potential of the cytoplasmic membrane (CM) energizes transport across the outer membrane, which requires an energy-transducing device, consisting of the proteins TonB, ExbB and ExbD, from the CM to the OM. Active transport across the CM is energized by ATP hydrolysis. Transport is regulated at the level of gene transcription. In Gram-negative bacteria, this is controlled by the Fur protein, in most gram-positive bacteria, by the DtxR protein. Fur and DtxR act as repressors when loaded with Fe2+. In the cytoplasm, iron is released from the siderophores by reduction to Fe2+, and the siderophores are either inactivated or secreted. The intracellular iron is built into heme and non-heme iron proteins, and a small proportion is incorporated into bacterioferritin, but most of the iron is present in a poorly defined state. Iron overload results in iron toxicity, mainly due to the formation of hydroxyl radicals that strongly react with all kinds of biomolecules, of which DNA damage has the most deleterious consequences.