Iron is an essential nutrient for all organisms. For pathogenic fungi, iron is essential for the success of infection. Thus, these organisms have developed high affinity iron uptake mechanisms to deal with metal deprivation imposed by the host. Siderophore production is one of the mechanisms that fungal pathogens employ for iron acquisition. Paracoccidioides spp. present orthologous genes encoding the enzymes necessary for the biosynthesis of hydroxamates, and plasma membrane proteins related to the transport of these molecules. All these genes are induced in iron deprivation. In addition, it has been observed that Paracoccidioides spp. are able to use siderophores to scavenge iron. Here we observed that addition of the xenosiderophore ferrioxamine B FOB) to P. brasiliensis culture medium results in repression (at RNA and protein levels) of the SidA, the first enzyme of the siderophore biosynthesis pathway. Furthermore, SidA activity was reduced in the presence of FOB, suggesting that P. brasiliensis blocks siderophores biosynthesis and can explore siderophores in the environment to scavenge iron. In order to support the importance of siderophores on Paracoccidioides sp. life and infection cycle, silenced mutants for the sidA gene were obtained by antisense RNA technology. The obtained AsSidA strains displayed decreased siderophore biosynthesis in iron deprivation conditions and reduced virulence to an invertebrate model.

中文翻译：

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巴西副球孢子菌铁载体生物合成的分子特征。

铁是所有生物体的必需营养素。对于病原真菌来说，铁对于感染的成功至关重要。因此，这些生物体已经发展出高亲和力的铁吸收机制来应对宿主施加的金属剥夺。铁载体的产生是真菌病原体获取铁的机制之一。副球孢子菌属 存在编码异羟肟酸生物合成所必需的酶的直系同源基因，以及与这些分子的运输相关的质膜蛋白。所有这些基因都是在铁缺乏时被诱导的。此外，还观察到副球孢子菌属（Paracoccidioides spp）。能够利用铁载体来清除铁。在这里，我们观察到向巴西假单胞菌培养基中添加异铁素铁胺 B (FOB) 会导致铁载体生物合成途径的第一种酶 SidA 的抑制（在 RNA 和蛋白质水平）。此外，在 FOB 存在的情况下，SidA 活性降低，表明巴西 P. brasiliensis 阻断铁载体生物合成，并且可以探索环境中的铁载体来清除铁。为了支持副球孢子菌铁载体的重要性。通过反义RNA技术获得了sidA基因的沉默突变体。获得的 AsSidA 菌株在缺铁条件下表现出铁载体生物合成减少，并且对无脊椎动物模型的毒力降低。