TRANSPORTATION ZINC IN ASPERGILLUS FUMIIGATUS: A SYSTEM REGULATED BY ZINC AND PH.Author:
VICENTEFRANQUEIRA RODRIGUEZ ROCIO.
Year:
2005.
University:
SALAMANCA [
www.usal.es].
Place of defense: DEPARTAMENTO MICROBIOLOGIA Y GENETICA.
Place of preparation: DEPARTAMENTNO DE MICROBIOLOGIA Y GENETICA.
Summary: Aspergillus fumigatus is an opportunistic pathogen fungus. This thesis proposes mechanisms of uptake and transport of zinc as targets for the design of new antifungal agents against specific A. Fumigatus. It had previously been shown that this trace element is crucial to the growth and development of the fungus and that the antigen inmunodominante, ASPF2, is expressed only in the absence of zinc (*). We have cloned and sequenced 3 genes (zrfA, zrfB and zrfC) encoding permeasas membrane, belonging to the family of carriers HTML (Zrt, Irt-like Protein). ZrfC is the only species that seems to have binding domains of zinc into the extracellular space. While the three formed special channels for the passage of zinc inside the cell. The regulation of gene expression zrfA, zrfB and zrfC depends on the concentration of zinc as the pH of the medium. So, although all of them are expressed only in limited ways in zinc zrfA and zrfB do preferably in the acidic (**) and zrfC only means neutral or basic. This work has helped determine that the gene coding for ASPF2 shares with the promoter gene zrfC and also expressed preferentially in basic means limiting zinc. The deletion of genes zrfA, zrfB and zrfC in unison determines serious defects in the growth of the fungus becoming fatal means limiting zinc. In addition, virulence tests conducted with the triple mutant strain, in murine models of invasive aspergillosis, have shown that this strain is completely avirulenta.
