Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets

Abstract

Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding of the fungal life cycle, functional genomics, proteomics, and gene mapping have enabled the identification of new drug targets to treat these potentially deadly infections. In this paper, we examine amino acid transport mechanisms and metabolism as potential drug targets to treat invasive fungal infections, including pathogenic yeasts, such as species of Candida and Cryptococcus, as well as molds, such as Aspergillus fumigatus. We also explore the mechanisms by which amino acids may be exploited to identify novel drug targets and review potential hurdles to bringing this approach into clinical practice.

Keywords: amino acid transporters; antifungal targets; cispentacin; icofungipen; metabolism; sinefungin.

Figure 1

Comparative structures of proline, cispentacin, and icofungipen.

Figure 2

Comparative structures of S-adenosylmethionine and sinefungin.