AI Article Synopsis
- Suramin, developed by Bayer in 1916, is still the preferred treatment for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense.
- The study found that resistance to suramin in T. brucei can occur quickly and is linked to changes in the variant surface glycoprotein (VSG) that trypanosomes use to evade the immune system.
- Reintroducing the original VSG gene in resistant trypanosomes restored their sensitivity to suramin, marking the first evidence of a connection between antigenic variation and drug resistance in these parasites.
Article Abstract
Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream-form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T. brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSG , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T. brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/mmi.13854 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transforming the chemotherapy of human African trypanosomiasis.
Clin Microbiol Rev
January 2025
School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement.
View Article and Find Full Text PDFCryo-EM structure of Nipah virus L-P polymerase complex.
Nat Commun
December 2024
Beijing Life Science Academy, Beijing, China.
Nipah virus (NiV) is a non-segmented, negative-strand (NNS) RNA virus, belonging to Paramyxoviridae. The RNA polymerase complex, composed of large (L) protein and tetrameric phosphoprotein (P), is responsible for genome transcription and replication by catalyzing NTP polymerization, mRNA capping and cap methylation. Here, we determine the cryo-electron microscopy (cryo-EM) structure of fully bioactive NiV L-P polymerase complex at a resolution of 3.
View Article and Find Full Text PDFFrom Proteome to Potential Drugs: Integration of Subtractive Proteomics and Ensemble Docking for Drug Repurposing against RND Superfamily Proteins.
Int J Mol Sci
July 2024
Laboratorio de Bioinformática y Química Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Católica del Maule, Talca 3480094, Chile.
() poses a significant threat as a nosocomial pathogen due to its robust resistance mechanisms and virulence factors. This study integrates subtractive proteomics and ensemble docking to identify and characterize essential proteins in , aiming to discover therapeutic targets and repurpose commercial existing drugs. Using subtractive proteomics, we refined the dataset to discard redundant proteins and minimize potential cross-interactions with human proteins and the microbiome proteins.
View Article and Find Full Text PDFMolecular characterization of trypanocide-resistant strains derived from a single field isolate of Trypanosoma evansi.
Vet Parasitol
August 2024
Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency, Cibinong Science Center, JL. Raya Jakarta - Bogor Km. 46, Bogor, West Jawa Province 16911, Indonesia.
Four strains (SB-PR, SB-RS, SB-RD, and SB-RM) of Trypanosoma evansi (T. evansi) were used in this study. SB-PR is known to be trypanocide-sensitive, while the others are trypanocide-resistant to suramin, diminazene diaceturate, and melarsomine hydrochloride, respectively.
View Article and Find Full Text PDFA Landscape on Lymphatic Filariasis with its Effects and Recent Advanced Treatments.
Recent Adv Antiinfect Drug Discov
May 2024
Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India.
Lymphatic filariasis is an infection caused by parasites that poses a significant health, social, and economic burden, affecting a vast population that exceeds 120 million individuals globally. The Etiology of the infection is attributed to three nematode parasites, namely Wuchereria bancrofti, B. timori, and Brugia malayi, as well as which are phylogenetically related.
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!