Hemoglobin uptake by Paracoccidioides spp. is receptor-mediated.

Autor: Bailão EF; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Unidade Universitária de Iporá, Universidade Estadual de Goiás, Iporá, Goiás, Brazil; Programa de Pós Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, Brasília, Distrito Federal, Brazil., Parente JA; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil., Pigosso LL; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil., de Castro KP; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil., Fonseca FL; Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil., Silva-Bailão MG; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Programa de Pós Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, Brasília, Distrito Federal, Brazil., Báo SN; Laboratório de Microscopia Eletrônica, Universidade de Brasília, Distrito Federal, Brazil., Bailão AM; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil., Rodrigues ML; Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil; Fundação Oswaldo Cruz - Fiocruz, Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil., Hernandez O; Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia; Facultad de Ciencias de la Salud, Institución Universitaria Colegio Mayor de Antioquia, Medellín, Colombia., McEwen JG; Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia; Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia., Soares CM; Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2014 May 15; Vol. 8 (5), pp. e2856. Date of Electronic Publication: 2014 May 15 (Print Publication: 2014).
DOI: 10.1371/journal.pntd.0002856
Abstrakt: 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.
Databáze: MEDLINE
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