Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.

Bibliographic Details
Main Author: Gonçalves, Adriana F.
Publication Date: 2024
Other Authors: Lima-Pinheiro, Ana, Teixeira, Miguel, Cassiano, Gustavo Capatti, Cravo, Pedro, Ferreira, Pedro Eduardo
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/165883
Summary: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support was provided by grants from Portuguese National funds, through the Foundation for Science and Technology (FCT) -project UIDB/50026/2020 (DOI 10.54499/UIDB/50026/2020), UIDP/50026/2020 (DOI 10.54499/UIDP/50026/2020) and LA/P/0050/2020 (DOI 10.54499/LA/P/0050/2020), PTDC/SAU-PAR/2766/2021 to PF and 2022.12892.BD to AG. Copyright © 2024 Gonçalves, Lima-Pinheiro, Teixeira, Cassiano, Cravo and Ferreira.
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spelling Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.HumansPlasmodium falciparum/geneticsProteasome Endopeptidase Complex/geneticsAntimalarials/pharmacologyArtemisinins/pharmacologyMalaria, Falciparum/parasitologyMutationProtozoan Proteins/geneticsQR MicrobiologyQR180 ImmunologyRM Therapeutics. PharmacologyInfectious DiseasesGeneral Pharmacology, Toxicology and PharmaceuticsParasitologySDG 3 - Good Health and Well-beingThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support was provided by grants from Portuguese National funds, through the Foundation for Science and Technology (FCT) -project UIDB/50026/2020 (DOI 10.54499/UIDB/50026/2020), UIDP/50026/2020 (DOI 10.54499/UIDP/50026/2020) and LA/P/0050/2020 (DOI 10.54499/LA/P/0050/2020), PTDC/SAU-PAR/2766/2021 to PF and 2022.12892.BD to AG. 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.Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)Vector borne diseases and pathogens (VBD)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNGonçalves, Adriana F.Lima-Pinheiro, AnaTeixeira, MiguelCassiano, Gustavo CapattiCravo, PedroFerreira, Pedro Eduardo2024-04-06T00:38:54Z20242024-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/165883eng2235-2988PURE: 84383252https://doi.org/10.3389/fcimb.2024.1342856info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-31T01:52:14Zoai:run.unl.pt:10362/165883Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:50:58.840578Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
title Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
spellingShingle Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
Gonçalves, Adriana F.
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
title_short Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
title_full Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
title_fullStr Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
title_full_unstemmed Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
title_sort Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin.
author Gonçalves, Adriana F.
author_facet Gonçalves, Adriana F.
Lima-Pinheiro, Ana
Teixeira, Miguel
Cassiano, Gustavo Capatti
Cravo, Pedro
Ferreira, Pedro Eduardo
author_role author
author2 Lima-Pinheiro, Ana
Teixeira, Miguel
Cassiano, Gustavo Capatti
Cravo, Pedro
Ferreira, Pedro Eduardo
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)
Vector borne diseases and pathogens (VBD)
Global Health and Tropical Medicine (GHTM)
Instituto de Higiene e Medicina Tropical (IHMT)
RUN
dc.contributor.author.fl_str_mv Gonçalves, Adriana F.
Lima-Pinheiro, Ana
Teixeira, Miguel
Cassiano, Gustavo Capatti
Cravo, Pedro
Ferreira, Pedro Eduardo
dc.subject.por.fl_str_mv 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
topic 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
description The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Financial support was provided by grants from Portuguese National funds, through the Foundation for Science and Technology (FCT) -project UIDB/50026/2020 (DOI 10.54499/UIDB/50026/2020), UIDP/50026/2020 (DOI 10.54499/UIDP/50026/2020) and LA/P/0050/2020 (DOI 10.54499/LA/P/0050/2020), PTDC/SAU-PAR/2766/2021 to PF and 2022.12892.BD to AG. Copyright © 2024 Gonçalves, Lima-Pinheiro, Teixeira, Cassiano, Cravo and Ferreira.
publishDate 2024
dc.date.none.fl_str_mv 2024-04-06T00:38:54Z
2024
2024-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/165883
url http://hdl.handle.net/10362/165883
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2235-2988
PURE: 84383252
https://doi.org/10.3389/fcimb.2024.1342856
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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