Membrane and cell wall targets in Aspergillus fumigatus

Antifungal drugs directed against the human opportunistic fungal pathogen A spergillus fumigatus are limited in number and ergosterol-targeted: the pol yenes bind to the membrane ergosterol and the azoles block the ergosterol b iosynthesis pathway. The efficacy of the drugs currently available for clin ical use (amphotericin B and itraconazole) is limited and the frequent occu rrence of therapeutic failures in the treatment of invasive aspergillosis e mphasizes the need for the development of new agents. Cell wall biosyntheti c pathways have been recognized for a long time as essential and unique spe cific drug targets. Recent studies of the chemical organization of the cell wall of A. fumigatus together with comparative analysis of yeast cell wall data have shown that beta1-3 glucan branching and chitin-beta1-3 glucan bi nding are essential exocellular enzymatic steps in cell wall biosynthesis. The enzymes involved in the biosynthesis and remodeling of cell wall polysa ccharides especially in A. fumigatus are reviewed. (C) 2001 Harcourt Publis hers Ltd.