Functions as Targets for Chemotherapy

摘要: It is a goal of antimicrobial drug discovery efforts to identify pathways that are unique, conserved, and essential in microbial pathogens, with the hope of developing agents with selective toxicity. For viruses and eukaryotic parasites, this goal becomes quite challenging, because the physiological processes used by these pathogens are often very similar to those of their hosts. In this chapter, we suggest that a significant number of essential physiological processes carried out by mitochondria of eukaryotic pathogens are likely to be sufficiently divergent from the mitochondria of their hosts and that these could be fruitfully explored in drug discovery endeavors. Eukaryotic pathogens, comprising a vast group of organisms including protozoa, fungi, and invertebrate animals, take an enormous toll on the health and economy of the world’s population. In general, we have fairly limited means available to counter these pathogens, often with drugs that have low therapeutic indices and high toxicity. While oxidative phosphorylation to generate ATP is the most obvious role for mitochondria, it is clear that these organelles play a critical role in many other metabolic processes such as calcium homeostasis, amino acid metabolism, isoprenoid synthesis, lipid metabolism, and heme synthesis. Indeed, there are cell type-and species-specific functions associated with mitochondria. Furthermore, the central role played by mitochondria in life and death decisions by the metazoan cells has become increasingly clear, resulting in a resurgence of interest in