Abstract
The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct adaptations to the differences in nutritional availabilities, either relying on biosynthetic pathways or by salvaging metabolites from their host. Pantothenate (Pan, vitamin B5) is the precursor for the synthesis of an essential cofactor, coenzyme A (CoA), but among the apicomplexans, only the coccidian subgroup has the ability to synthesize Pan. While the pathway to synthesize CoA from Pan is largely conserved across all branches of life, there are differences in the redundancy of enzymes and possible alternative pathways to generate CoA from Pan. Impeding the scavenge of Pan and synthesis of Pan and CoA have been long recognized as potential targets for antimicrobial drug development, but in order to fully exploit these critical pathways, it is important to understand such differences. Recently, a potent class of pantothenamides (PanAms), Pan analogs, which target CoA-utilizing enzymes, has entered antimalarial preclinical development. The potential of PanAms to target multiple downstream pathways make them a promising compound class as broad antiparasitic drugs against other apicomplexans. In this review, we summarize the recent advances in understanding the Pan and CoA biosynthesis pathways, and the suitability of these pathways as drug targets in Apicomplexa, with a particular focus on the cyst-forming coccidian, Toxoplasma gondii, and the haemosporidian, Plasmodium falciparum.
Funder
Radboud Universiteit
Netherlands Organization for International Cooperation in Higher Education
iGE3
European Research Council
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
Reference160 articles.
1. The global burden of congenital toxoplasmosis: a systematic review;PR Torgerson;Bull World Health Organ,2013
2. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium;W Checkley;Lancet Infect Dis,2015
3. WHO. World Malaria Report. 2020:2020.
4. Long-term persistence of Toxoplasma gondii in tissues of pigs inoculated with T gondii oocysts and effect of freezing on viability of tissue cysts in pork;JP Dubey;Am J Vet Res,1988
5. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts;JP Dubey;Clin Microbiol Rev,1998
Cited by
16 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献