Chapter 15. Targets for Antifungal Drug Discovery

This chapter discusses the recent work on existing antifungal agents, new agents under development, and on new potential targets for antifungal drug design. During recent times, it has been observed that the incidence of fungal infections has increased and that a broader spectrum of fungal infections has emerged. These changes have been attributed to the intensive use of chemotherapy for bacterial infections, wider usage of catheterization, and immune suppression because of organ transplantation and other medical procedures. Many reports describe infections by fungi not previously recognized as human pathogens as well as previously unknown modes of evasion of immune surveillance used by fungi. The advent of AIDS has introduced an additional group of immune compromised patients who are predisposed to fungal infections with a unique pattern of infection. For example, in this patient population oral and esophageal Candida infections are prevalent, while Cryptococcus has emerged as a major pathogen. As a result of these developments, the relative importance of the fungal pathogens has changed in recent times. While progress is continuing in the study of existing agents and the development of new ones, developments in genetic methodology and advances in knowledge of the biochemistry of fungi offer the prospect of identifying new antifungal targets. Gene disruption is proving to be a useful technique for the identification of genes that are either essential for the life of the organism or are responsible for virulence. Unique structural characteristics of fungal tubulins, secreted proteinases, elongation factors, and membrane-bound receptors are being investigated in the search for novel antifungal targets.