ABSTRACT

The occurrence of fungal infections has escalated significantly in recent years. and this increase is particularly profound in those immunocompromised by disease or therapies. Unfortunately. the number of antifungal drugs available for combating fungal infections is limited. The paucity of effective agents is due in large part to the high degree of relatedness between the biochemical machinery of fungi and the mammalian host. In this regard, only a few suitable targets with the necessary specificity have been successfully utilized in antifungal development, and these are primarily associated with fungal cell wall and membrane biosynthesis. The most effective antifungal agents against these targets are azole derivatives and amphotericin B. While these agents are commonly employed. their usage presents a number of shortcomings including toxicity, fungistatic versus fungicidal activity, and the appearance of drug-resistant organisms. Thus, there is an urgent need to augment the number of suitable targets in order to detect and develop novel and effective antifungal agents. This need is being addressed by major research efforts to uncover potential targets and companion agents. Such investigations are supported in part by new approaches, as well as more traditional methodologies, designed to more rapidly identify and verify novel targets. The aim of the following discussion is to present an overview of such approaches and promising antifungal targets.