On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria
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Publication Date: | 2022 |
Format: | Article |
Language: | eng |
Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
Download full: | http://hdl.handle.net/10362/142753 |
Summary: | Copyright © 2022. Published by Elsevier B.V. |
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On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malariaParasitologyInfectious DiseasesSDG 3 - Good Health and Well-beingCopyright © 2022. Published by Elsevier B.V.Malaria is a devastating disease that still claims over half a million lives every year, mostly in sub-Saharan Africa. One of the main barriers to malaria control is the evolution and propagation of drug-resistant mutant parasites. Knowing the genes and respective mutations responsible for drug resistance facilitates the design of drugs with novel modes of action and allows predicting and monitoring drug resistance in natural parasite populations in real-time. The best way to identify these mutations is to experimentally evolve resistance to the drug in question and then comparing the genomes of the drug-resistant mutants to that of the sensitive progenitor parasites. This simple evolutive concept was the starting point for the development of a paradigm over the years, based on the use of the rodent malaria parasite Plasmodium chabaudi to unravel the genetics of drug resistance in malaria. It involves the use of a cloned parasite isolate (P. chabaudi AS) whose genome is well characterized, to artificially select resistance to given drugs through serial passages in mice under slowly increasing drug pressure. The end resulting parasites are cloned and the genetic mutations are then discovered through Linkage Group Selection, a technique conceived by Prof. Richard Carter and his group, and/or Whole Genome Sequencing. The precise role of these mutations can then be interrogated in malaria parasites of humans through allelic replacement experiments and/or genotype-phenotype association studies in natural parasite populations. Using this paradigm, all the mutations underlying resistance to the most important antimalarial drugs were identified, most of which were pioneering and later shown to also play a role in drug resistance in natural infections of human malaria parasites. This supports the use of P. chabaudi a fast-track predictive model to identify candidate genetic markers of resistance to present and future antimalarial drugs and improving our understanding of the biology of resistance.Vector borne diseases and pathogens (VBD)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNCravo, Pedro2022-08-01T22:24:45Z2022-122022-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/142753eng1383-5769PURE: 45531196https://doi.org/10.1016/j.parint.2022.102623info: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:RCAAP2024-05-22T18:04:10Zoai:run.unl.pt:10362/142753Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:34:43.531675Repositórios 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 |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
title |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
spellingShingle |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria Cravo, Pedro Parasitology Infectious Diseases SDG 3 - Good Health and Well-being |
title_short |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
title_full |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
title_fullStr |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
title_full_unstemmed |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
title_sort |
On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria |
author |
Cravo, Pedro |
author_facet |
Cravo, Pedro |
author_role |
author |
dc.contributor.none.fl_str_mv |
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 |
Cravo, Pedro |
dc.subject.por.fl_str_mv |
Parasitology Infectious Diseases SDG 3 - Good Health and Well-being |
topic |
Parasitology Infectious Diseases SDG 3 - Good Health and Well-being |
description |
Copyright © 2022. Published by Elsevier B.V. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-08-01T22:24:45Z 2022-12 2022-12-01T00:00:00Z |
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/10362/142753 |
url |
http://hdl.handle.net/10362/142753 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1383-5769 PURE: 45531196 https://doi.org/10.1016/j.parint.2022.102623 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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