AI Article Synopsis
- * The study found that T. brucei brucei uses two highly efficient nucleobase transporters, H1 and H4, to absorb allopurinol, which helps prevent the establishment of drug resistance.
- * Long-term exposure to allopurinol did not alter the transport efficiency or uptake mechanisms of these transporters, allowing the parasite to continue thriving on hypoxanthine as a purine source.
Article Abstract
Allopurinol is a hypoxanthine analogue used to treat Leishmania infections that also displays activity against the related parasite Trypanosoma brucei. We have investigated the ease by which resistance to this drug is established in Trypanosoma brucei brucei and correlated this to the mechanisms by which it is accumulated by the parasite. Long-term exposure of procyclic T. b. brucei to 3mM allopurinol did not induce resistance. This appears to be related to the fact that allopurinol was taken up through two distinct nucleobase transporters, H1 and H4, both with high affinity for the drug. The apparent Km for [3H]allopurinol transport by H4 (2.1+/-0.4 microM) was determined by expressing the encoding gene in Saccharomyces cerevisiae. Long-term allopurinol exposure did not change Km (hypoxanthine), Ki (allopurinol), or Vmax values of either H1 or H4 transporters and the cells retained their ability to proliferate with hypoxanthine as sole purine source. This study shows that transport-related resistance to purine antimetabolites is not easily induced in Trypanosoma spp. as long as uptake is mediated by multiple transporters.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exppara.2004.11.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Isolation and Total Synthesis of Ukabamide, an Antitrypanosomal Lipopeptide from a Marine sp. Cyanobacterium.
Org Lett
January 2025
Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
Human African trypanosomiasis (HAT) is one of the most lethal of the neglected tropical diseases. While the discovery of a novel antitrypanosomal drug is highly desired, the creation of a superior lead compound is challenging. Herein we report ukabamide (), which was isolated from a marine sp.
View Article and Find Full Text PDF3'-deoxytubercidin: A potent therapeutic candidate for the treatment of Surra and Dourine.
Int J Parasitol Drugs Drug Resist
January 2025
Laboratory of Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp, 2610, Wilrijk, Belgium. Electronic address:
Surra and Dourine are widespread diseases caused by two protozoan parasites Trypanosoma brucei evansi and Trypanosoma brucei equiperdum, respectively. A wide range of animals including camels, horses, cattle and buffaloes are susceptible to infection. These diseases pose a significant socio-economic burden, primarily due to the limited therapeutic options and the complications associated with toxicity and drug resistance, making disease management particularly challenging.
View Article and Find Full Text PDFAntiparasitic Activities of Plants from the Traditional Senegalese Pharmacopoeia: Isolation of Antitrypanosomal and Antileishmanial ellagic acid derivatives from Terminalia avicennioides.
Chem Biodivers
January 2025
University of Lille: Universite de Lille, UMR BioEcoAgro, 3 rue du Professeur Laguesse, 59800, LILLE, FRANCE.
Parasitic diseases such as trypanosomiasis and leishmaniasis pose significant health challenges in Africa. The Senegalese Pharmacopoeia, known for its many medicinal plants with anti-infectious properties, can be a source of antiparasitic natural products. This study aimed to evaluate the in vitro antiparasitic activities of 33 methanolic extracts from 24 ethnopharmacologically selected plants against Trypanosoma brucei brucei and Leishmania mexicana mexicana, as well as their cytotoxic activities on WI-38 cells.
View Article and Find Full Text PDFNanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.
Nat Commun
January 2025
University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, United Kingdom.
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres.
View Article and Find Full Text PDFManipulation of mitochondrial poly(A) polymerase family proteins in impacts mRNA termini processing.
Front Parasitol
January 2024
Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, United States.
RNA-specific nucleotidyltransferases (rNTrs) add nontemplated nucleotides to the 3 end of RNA. Two noncanonical rNTRs that are thought to be poly(A) polymerases (PAPs) have been identified in the mitochondria of trypanosomes - KPAP1 and KPAP2. KPAP1 is the primary polymerase that adds adenines (As) to trypanosome mitochondrial mRNA 3 tails, while KPAP2 is a non-essential putative polymerase whose role in the mitochondria is ambiguous.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!