On the contribution of the rodent model Plasmodium chabaudi for understanding the genetics of drug resistance in malaria

Bibliographic Details
Main Author: Cravo, Pedro
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.
id RCAP_ccfccbc220e1cd3e541650135acfba79
oai_identifier_str oai:run.unl.pt:10362/142753
network_acronym_str RCAP
network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository_id_str https://opendoar.ac.uk/repository/7160
spelling 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
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
instacron:RCAAP
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
_version_ 1833596809381937152