{"title":"Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids.","authors":"Anders Hofer","doi":"10.1093/femsre/fuad020","DOIUrl":null,"url":null,"abstract":"<p><p>African sleeping sickness, Chagas disease, and leishmaniasis are life-threatening diseases that together affect millions of people around the world and are caused by different members of the protozoan family Trypanosomatidae. The most studied member of the family is Trypanosoma brucei, which is spread by tsetse flies and causes African sleeping sickness. Nucleotide metabolism in T. brucei and other trypanosomatids is significantly different from that of mammals and was recognized as a target for chemotherapy already in the 1970-1980s. A more thorough investigation of the nucleotide metabolism in recent years has paved the way for identifying nucleoside analogues that can cure T. brucei brain infections in animal models. Specific features of T. brucei nucleotide metabolism include the lack of de novo purine biosynthesis, the presence of very efficient purine transporters, the lack of salvage pathways for CTP synthesis, unique enzyme localizations, and a recently discovered novel pathway for dTTP synthesis. This review describes the nucleotide metabolism of T. brucei, highlights differences and similarities to other trypanosomatids, and discusses how to exploit the parasite-specific features for drug development.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":"47 3","pages":""},"PeriodicalIF":10.1000,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208901/pdf/","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEMS microbiology reviews","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/femsre/fuad020","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
African sleeping sickness, Chagas disease, and leishmaniasis are life-threatening diseases that together affect millions of people around the world and are caused by different members of the protozoan family Trypanosomatidae. The most studied member of the family is Trypanosoma brucei, which is spread by tsetse flies and causes African sleeping sickness. Nucleotide metabolism in T. brucei and other trypanosomatids is significantly different from that of mammals and was recognized as a target for chemotherapy already in the 1970-1980s. A more thorough investigation of the nucleotide metabolism in recent years has paved the way for identifying nucleoside analogues that can cure T. brucei brain infections in animal models. Specific features of T. brucei nucleotide metabolism include the lack of de novo purine biosynthesis, the presence of very efficient purine transporters, the lack of salvage pathways for CTP synthesis, unique enzyme localizations, and a recently discovered novel pathway for dTTP synthesis. This review describes the nucleotide metabolism of T. brucei, highlights differences and similarities to other trypanosomatids, and discusses how to exploit the parasite-specific features for drug development.
期刊介绍:
Title: FEMS Microbiology Reviews
Journal Focus:
Publishes reviews covering all aspects of microbiology not recently surveyed
Reviews topics of current interest
Provides comprehensive, critical, and authoritative coverage
Offers new perspectives and critical, detailed discussions of significant trends
May contain speculative and selective elements
Aimed at both specialists and general readers
Reviews should be framed within the context of general microbiology and biology
Submission Criteria:
Manuscripts should not be unevaluated compilations of literature
Lectures delivered at symposia must review the related field to be acceptable