Hemoglobin uptake by Paracoccidioides spp. is receptor-mediated
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2014
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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 tumefaciensmediated
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.
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BAILÃO, Elisa Flávia Luiz Cardoso et al. Hemoglobin uptake by Paracoccidioides spp. is receptor-mediated. PLoS Neglected Tropical, San Francisco, v. 8, n. 5, e2856, 2014.