دورية أكاديمية
Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
| العنوان: | Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin. |
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| المؤلفون: | Gonçalves, Adriana F, Lima-Pinheiro, Ana, Teixeira, Miguel, Cassiano, Gustavo Capatti, Cravo, Pedro, Ferreira, Pedro E |
| المساهمون: | Vector borne diseases and pathogens (VBD), Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT) |
| سنة النشر: | 2024 |
| المجموعة: | Repositório da Universidade Nova de Lisboa (UNL) |
| مصطلحات موضوعية: | Humans, Plasmodium falciparum/genetics, Proteasome Endopeptidase Complex/genetics, Antimalarials/pharmacology, Artemisinins/pharmacology, Malaria, Falciparum/parasitology, Mutation, Protozoan Proteins/genetics, QR Microbiology, QR180 Immunology, RM Therapeutics. Pharmacology, Infectious Diseases, General Pharmacology, Toxicology and Pharmaceutics, Parasitology, SDG 3 - Good Health and Well-being |
| الوصف: | Copyright © 2024 Gonçalves, Lima-Pinheiro, Teixeira, Cassiano, Cravo and Ferreira. ; INTRODUCTION: Malaria parasites increasingly develop resistance to all drugs available in the market, hampering the goal of reducing malaria burden. METHODS: Herein, we evaluated the impact of a single-nucleotide variant, E738K, present in the 26S proteasome regulatory subunit rpn2 gene, identified in Plasmodium chabaudi resistant parasites. Plasmids carrying a functional rpn2 interspecies chimeric gene with 5' recombination region from P. falciparum and 3' from P. chabaudi were constructed and transfected into Dd2 P. falciparum parasites. RESULTS AND DISCUSSION: The 738K variant parasite line presented increased parasite survival when subjected to dihydroartemisinin (DHA), as well as increased chymotrypsin-like activity and decreased accumulation of polyubiquitinated proteins. We thus conclude that the ubiquitin-proteasome pathway, including the 738K variant, play an important role in parasite response to DHA, being the first report of a mutation in a potential DHA drug target enhancing parasite survival and contributing to a significant advance in the understanding the biology of artemisinin resistance. ; publishersversion ; published |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2235-2988 |
| العلاقة: | PURE: 84383252; PURE UUID: 2fc5e584-4dbb-42a4-b093-7383ef3e3cae; PubMed: 38404287; PubMedCentral: PMC10884193; Scopus: 85185512905; WOS: WOS:001168721000001; ORCID: /0000-0003-1675-4504/work/155298910; http://hdl.handle.net/10362/165883Test; https://doi.org/10.3389/fcimb.2024.1342856Test |
| DOI: | 10.3389/fcimb.2024.1342856 |
| الإتاحة: | https://doi.org/10.3389/fcimb.2024.1342856Test http://hdl.handle.net/10362/165883Test |
| حقوق: | openAccess |
| رقم الانضمام: | edsbas.B38FDDA8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22352988 |
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| DOI: | 10.3389/fcimb.2024.1342856 |