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首页> 外文期刊>PLOS Neglected Tropical Diseases >Hemoglobin Uptake by Paracoccidioides spp. Is Receptor-Mediated
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Hemoglobin Uptake by Paracoccidioides spp. Is Receptor-Mediated

机译：副球菌对血红蛋白的吸收。是受体介导的

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Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms.
机译：铁对于感染期间真菌病原体的繁殖至关重要。铁的可用性因其与宿主蛋白的结合而受到限制。真菌病原体已经进化出不同的机制从宿主获取铁。但是，关于副球菌如何结合并代谢该离子知之甚少。在这项工作中，由Paracoccidioides spp使用的宿主铁源。被调查了。在含铁分子血红素和血红蛋白的存在下，观察到健壮的真菌生长。副球菌属具有溶血活性并具有内原卟啉环的能力。使用实时PCR和nanoUPLC-MSE蛋白质组学方法，在存在血红蛋白的情况下，真菌的生长显示出对编码假定的血红蛋白受体的转录本的正向调节作用，此外还诱导了氨基酸代谢和代谢所需的蛋白质。液泡蛋白降解。实际上，一种血红蛋白受体直向同源物Rbt5被鉴定为表面GPI锚定的蛋白，可在体外识别血红素，原卟啉和血红蛋白。反义RNA技术和根癌农杆菌介导的转化用于产生有丝分裂稳定的Pbrbt5突变体。与亲本菌株相比，敲低菌株在巨噬细胞内部和小鼠脾脏中的存活率较低，这表明Rbt5可能是一种致病因子。总而言之，我们的数据表明Paracoccidioides spp。可以最有可能通过受体介导的途径将血红蛋白用作铁源，这可能与致病机制有关。

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