18 - Comparative aspects of nucleotide and amino-acid metabolism in toxoplasma gondii and other apicomplexa

Abstract

Nucleotides and amino acids are of fundamental importance in the replication and development of Toxoplasma gondii and other apicomplexan parasites. Nucleotides are in particular essential for replication of DNA and transcription of RNA in rapidly dividing stages. Nucleotides are also essential in providing the cellular energy sources (ATP and GTP), and are involved in numerous other metabolic roles. Nucleotides are either synthesized from small molecules and amino acids, or they are acquired via salvage pathways from preformed host-derived nucleobases and nucleosides. The apicomplexan parasites considered in this chapter, Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum, are important pathogens of humans that cause significant morbidity and mortality. Notably, current treatment strategies in human infections caused by T. gondii or P. falciparum are based on blocking the accumulation of nucleotides. This validated approach to chemotherapy highlights the significance of further research to dissect details of nucleotide metabolism in the Apicomplexa as well as the potential for this research to lead to the development of new treatments.