Estudo da homeostase de zinco no fungo patogênico Histoplasma capsulatum var. capsulatum: Abordagens proteômica e funcional

• Autor(a) principal: Siqueira, Janaina Gomes de
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/001300000d02w
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/6699
• topic: Privação de zinco; Infecção; Transportador de zinco; Metal deprivation; Infection; Zinc transporter; CIENCIAS BIOLOGICAS

Histoplasma capsulatum var. capsulatum is a pathogenic fungus that causes the systemic disease known as histoplasmosis. This mycosis presents endemicity in the regions of the Mississippi and Ohio rivers in the United States, also found in several countries of South America. In Brazil, the number of people infected by this fungus has been growing in recent years, especially in immunocompromised people. H. capsulatum is a thermodymorphic microorganism, found in two morphotypes: mycelium at 25ºC and yeast at 37ºC. During the infection process the pathogenic microorganism needs to obtain nutrients so that it grows and develops within the tissue of the host. Among the essential nutrients, zinc is an essential metal ion, used in the maintenance of numerous metabolic pathways. Zinc is used as catalytic and structural cofactor of numerous metalloproteins. Zinc uptake is characterized as a virulence factor in H. capsulatum. In order to study the molecular mechanisms of zinc homeostasis in H. capsulatum, the in silico analysis of zinc homeostasis related proteins. The ZafA transcription factor, which acts on the regulation of genes in response to the zinc level in the medium and the transcription factor PacC that regulates genes in response to pH, were also found. ZrfA and ZrfC membrane transporters were also found ZrfF, ZrcA and ZrcC vacuolar transporters. The transcriptional profile analysis of these genes was measured by RT-PCR in infected macrophages and in vitro. During the infection the ZafA and ZrfA genes were induced, suggesting that these genes were expressed in order to supply the fungal cell with zinc, due to the metal deficiency caused by the infection. In vitro, ZafA, ZrfC, ZrfF, ZrcA and ZrcC were induced at zinc deprivation condition, compared with control condition. According with proteomic data of fungus under conditions of zinc deprivation, it was suggested the induction of proteins related to rescue, defense and virulence, related mainly to oxidative stress, besides other metabolic pathways such as gluconeogenesis. These data suggest that the fungus undergoes a metabolic remodeling in response to the oxidative stress caused by zinc deprivation.