Estudo a homeostase de cobre no fungo patogênico histoplasma capsulatum

• Autor(a) principal: Tristão, Gabriel Brum
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000007xnh
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9384
• topic: Homeostase; Cobre; Metais; Histoplasma; Homeostasis; Copper; Metals; CIENCIAS BIOLOGICAS::MICROBIOLOGIA

Histoplasma capsulatum is a thermodymorphic pathogenic fungus that causes systemic mycosis known as histoplasmosis. This fungus grows as mycelium at temperatures around 25°C and as yeast at 37°C. During the infectious process, pathogenic microorganisms must obtain nutrients from the host in order to survive in infected tissues. Among these nutrients, copper is an essential metal ion, because it participates in oxidation/reduction reactions, in energy production, in the transport of electrons, its cofactor of many enzymes and metalloproteins and is required for energy and melanin production. Copper excess however, it is toxic due to the fact that produces reactive oxygen species, dislocates other metals from metalloproteins, causes damage to lipids and DNA, so because of this H. capsulatum must maintain the homeostasis of this metal during infection. We observed here that H. capsulatum, through the transcriptional levels of Ctr4, Mac1, Crp1 and Ace1, during the infectious process in macrophages, faces an environment of copper overload imposed by the host cells via copper ATPase ATP7a. This copper excess shown to be INF-ɣ and time dependent, because when macrophages are not stimulated by INF-ɣ and in greater times of infection, they impose a restrictive copper environment instead, during the infection. H. capsulatum uses the Crp1 copper efflux pump in order to respond this toxic copper milieu, since mutant yeasts for Crp1 were unable to grow at high levels of the metal. Despite the importance of Crp1 for the fungus in this context, it appears that Crp1 is not strictly necessary for the total virulence of the fungus, leading us to infer that other proteins may also be exerting a Crp1-like function in H. capsulatum. It is clear once again that in the pathogen-host relationship copper plays a complex, highly dynamic and dependent on certain biological variables role.