Translation elongation-3-like factors: are they rational antifungal targets?

The occurrence of fungal infection has escalated significantly in recent years and is expected to continue to increase for the foreseeable future. Unfortunately, only a limited number of antifungal drugs are currently available partially due to a lack of suitable targets. The most commonly used antifungals target the same molecule in the cell membrane and, while efficacious, are either extremely toxic or susceptible to resistance. This article examines elongation factor-3, which is unique to fungi and essential for fungal cell survival and, thus, an attractive antifungal target. A search for inhibitors of this 'perfect target' led to identification of compounds (sordarins) which inhibited elongation factor-2, a protein with a mammalian homologue. Molecular analysis demonstrated why sordarins can specifically act against fungal elongation factor-2. This data questions the validity of pursuing genes as targets only if they are unique to fungi. Proteins that are homologous to elongation factor-3 are also discussed. The advances in molecular techniques and bioinformatics will allow the re-evaluation of targets previously thought to be unattractive. In addition, molecular genetics provides new and novel information on cellular processes that can potentially introduce new targets.