Survival of Aspergillus fumigatus in serum involves removal of iron from transferrin:: the role of siderophores
Survival of Aspergillus fumigatus in serum involves removal of iron from transferrin:: the role of siderophores
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DOI：
10.1128/iai.72.3.1402-1408.2004
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发表时间：
2004-03-01
影响因子：
3.1
通讯作者：
Moore, MM
中科院分区：
文献类型：
--
作者：
Hissen, AHT;Chow, JMT;Moore, MM
烟曲霉是一种丝状真菌，可导致免疫功能低下的个体的侵袭性疾病。A.尽管游离铁的浓度非常低，烟曲霉可以在含有高达80%的人血清的培养基中生长。本研究的目的是确定A.烟曲霉从血清铁结合蛋白转铁蛋白中获得铁。在缺铁最低必需培养基（MEM）中，A.全转铁蛋白（holoTf）或FeCl 3的加入支持了烟曲霉的生长，但脱铁转铁蛋白（apoTf）的加入不支持烟曲霉的生长。A.转铁蛋白的水解降解。在MEM-血清中发生烟曲霉毒素降解;然而，转铁蛋白降解直到对数生长期后期才发生。转铁蛋白不被A.在MEM-holoTf中孵育的烟曲霉。尿素聚丙烯酰胺凝胶电泳结果表明，在MEM-holoTf中，holoTf被烟曲霉完全转化为apoTf。在人血清中，所有的单铁转铁蛋白在8h内转化为apoTf。A.在MEM-sermn中生长8小时和在MEM-holoTf中生长12小时后，转铁蛋白被A.即使在物理上被12-kDa-截止膜分离时，烟曲霉也是如此。从A.两种主要的铁载体被鉴定为三乙酰镰孢菌素C和铁微菌素。三乙酰fusarinine C和ferricrocin从holoTf中去除铁的亲和力与ferrichrome相当。这些数据表明A.烟曲霉在体外人血清中的存活涉及铁载体介导的从转铁蛋白中除去铁。转铁蛋白的蛋白水解降解可能在铁的获得中起次要作用。
Aspergillus fumigatus is a filamentous fungus which can cause invasive disease in immunocompromised individuals. A. fumigatus can grow in medium containing up to 80% human serum, despite very low concentrations of free iron. The purpose of this study was to determine the mechanism by which A. fumigatus obtains iron from the serum iron-binding protein transferrin. In iron-depleted minimal essential medium (MEM), A. fumigatus growth was supported by the addition of holotransferrin (holoTf) or FeCl3 but not by the addition of apotransferrin (apoTf). Proteolytic degradation of transferrin by A. fumigatus occurred in MEM-serum; however, transferrin degradation did not occur until late logarithmic phase. Moreover, transferrin was not degraded by A. fumigatus incubated in MEM-holoTf. Urea polyacrylamide gel electrophoresis showed that in MEM-holoTf, holoTf was completely converted to apoTf by A.fumigatus. In human serum, all of the monoferric transferrin was converted to apoTf within 8 h. Siderophores were secreted by A. fumigatus after 8 h of growth in MEM-sermn and 12 h in MEM-holoTf. The involvement of small molecules in iron acquisition was confirmed by the fact that transferrin was deferrated by A. fumigatus even when physically separated by a 12-kDa-cutoff membrane. Five siderophores were purified from A. fumigatus culture medium, and the two major siderophores were identified as triacetylfusarinine C and ferricrocin. Both triacetylfusarinine C and ferricrocin removed iron from holoTf with an affinity comparable to that of ferrichrome. These data indicate that A. fumigatus survival in human serum in vitro involves siderophore-mediated removal of iron from transferrin. Proteolytic degradation of transferrin may play a secondary role in iron acquisition.