The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence
The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence
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DOI：
10.1128/iai.73.9.5493-5503.2005
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发表时间：
2005-09-01
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;Wan, ANC;Moore, MM
烟曲霉是侵袭性霉菌感染的主要原因，在世界各地免疫受损的人群中是一个严重的问题。我们先前已经证明，烟曲霉菌在血清中的存活可能与铁载体的分泌有关。在本研究中，我们鉴定并鉴定了烟曲霉菌的SIDA基因，该基因编码L-鸟氨酸N-5-加氧酶，这是羟甲酸铁载体生物合成的第一步。烟曲霉菌编码501个氨基酸的蛋白质，与其他真菌L-鸟氨酸N-5-加氧酶有显著的同源性。通过对烟曲霉菌株的缺失，获得了一株稳定的德尔塔斯达菌株。该菌株不能合成铁载体N‘，N“，N’‘-三乙酰褐藻氨酸C(TAF)和铁霉素。Delta sida品系在富营养液中的生长与野生型相同；但是，Delta sida品系不能在低铁定义的培养基或含有10%人血清的培养基中生长，除非添加TAF或Ferricrocin。亲本菌株和Delta SIDA菌株的铁还原活性没有显著差异，表明阻断铁载体的分泌并不会导致这一途径的上调。与亲本菌株不同，Delta SIDA菌株无法从人转铁蛋白中去除铁。构建了一株救援菌株(Delta SIDA+SIDA)，它能产生铁载体，并且在铁限制的培养基上与野生型的生长相同。与野生型和获救的菌株不同，Delta SIDA菌株在侵袭性曲霉病小鼠模型中是无毒的，这表明SIDA对于烟曲霉的毒力是必要的。
Aspergillus fumigatus is the leading cause of invasive mold infection and is a serious problem in immuno-compromised populations worldwide. We have previously shown that survival of A. fumigatus in serum may be related to secretion of siderophores. In this study, we identified and characterized the sidA gene of A. fumigatus, which encodes L-ornithine N-5-oxygenase, the first committed step in hydroxamate siderophore biosynthesis. A. fumigatus sidA codes for a protein of 501 amino acids with significant homology to other fungal L-ornithine N-5-oxygenases. A stable Delta sidA strain was created by deletion of A. fumigatus sidA. This strain was unable to synthesize the siderophores N',N",N'''-triacetylfusarinine C (TAF) and ferricrocin. Growth of the Delta sidA strain was the same as that of the wild type in rich media; however, the Delta sidA strain was unable to grow in low-iron defined media or media containing 10% human serum unless supplemented with TAF or ferricrocin. No significant differences in ferric reduction activities were observed between the parental strain and the Delta sidA strain, indicating that blocking siderophore secretion did not result in upregulation of this pathway. Unlike the parental strain, the Delta sidA strain was unable to remove iron from human transferrin. A rescued strain (Delta sidA + sidA) was constructed; it produced siderophores and had the same growth as the wild type on iron-limited media. Unlike the wild-type and rescued strains, the Delta sidA strain was avirulent in a mouse model of invasive aspergillosis, indicating that sidA is necessary for A. fumigatus virulence.