Membrane and cell wall targets in Aspergillus fumigatus

Abstract

Antifungal drugs directed against the human opportunistic fungal pathogen Aspergillus fumigatus are limited in number and ergosterol-targeted: the polyenes bind to the membrane ergosterol and the azoles block the ergosterol biosynthesis pathway. The efficacy of the drugs currently available for clinical use (amphotericin B and itraconazole) is limited and the frequent occurrence of therapeutic failures in the treatment of invasive aspergillosis emphasizes the need for the development of new agents. Cell wall biosynthetic pathways have been recognized for a long time as essential and unique specific 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 beta 1-3 glucan branching and chitin-beta 1-3 glucan binding are essential exocellular enzymatic steps in cell wall biosynthesis. The enzymes involved in the biosynthesis and remodeling of cell wall polysaccharides especially in A. fumigatus are reviewed.