Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.
Identifieur interne : 00E301 ( Main/Exploration ); précédent : 00E300; suivant : 00E302Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.
Auteurs : Melanie J. Shears [France] ; Cyrille Y. Botté [France] ; Geoffrey I. Mcfadden [Australie]Source :
- Molecular and biochemical parasitology [ 1872-9428 ]
Descripteurs français
- KwdFr :
- Acides gras (métabolisme), Antipaludiques (isolement et purification), Antipaludiques (pharmacologie), Apicoplastes (métabolisme), Découverte de médicament (tendances), Plasmodium (métabolisme), Recherche biomédicale (tendances), Vaccins contre le paludisme (immunologie), Vaccins contre le paludisme (isolement et purification).
- MESH :
- immunologie : Vaccins contre le paludisme.
- isolement et purification : Antipaludiques, Vaccins contre le paludisme.
- métabolisme : Acides gras, Apicoplastes, Plasmodium.
- pharmacologie : Antipaludiques.
- tendances : Découverte de médicament, Recherche biomédicale.
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Malaria Vaccines.
- chemical , isolation & purification : Antimalarials, Malaria Vaccines.
- chemical , metabolism : Fatty Acids.
- chemical , pharmacology : Antimalarials.
- metabolism : Apicoplasts, Plasmodium.
- trends : Biomedical Research, Drug Discovery.
Abstract
The malaria parasite Plasmodium possesses a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is essential for parasite survival, and harbors several plant-like metabolic pathways including a type II fatty acid synthesis (FASII) pathway. The FASII pathway was discovered in 1998, and much of the early research in the field pursued it as a therapeutic drug target. These studies identified a range of compounds with activity against bloodstage parasites and led to the localization and characterization of most enzymes in the pathway. However, when genetic studies revealed FASII was dispensable in bloodstage parasites, it effectively discounted the pathway as a therapeutic drug target, and suggested these compounds instead interfered with other processes. Interest in FASII then shifted toward its disruption for malaria prophylaxis and vaccine development, with experiments in rodent malaria models identifying a crucial role for the pathway in the parasite's transition from the liver to the blood. Unexpectedly however, the human malaria parasite P. falciparum was recently found to differ from rodent models and require FASII for mosquito stage development. This requirement blocked the production of the FASII-deficient forms that might be used as a genetically attenuated parasite vaccine, suggesting the pathway was also unsuitable as a vaccine target. This review discusses how perception of FASII has changed over time, and presents key findings about each enzyme in the pathway to identify remaining questions and opportunities for malaria control.
DOI: 10.1016/j.molbiopara.2015.03.004
PubMed: 25841762
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 003101
- to stream PubMed, to step Curation: 003007
- to stream PubMed, to step Checkpoint: 003007
- to stream Ncbi, to step Merge: 002415
- to stream Ncbi, to step Curation: 002415
- to stream Ncbi, to step Checkpoint: 002415
- to stream Main, to step Merge: 00F541
- to stream Main, to step Curation: 00E301
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.</title><author><name sortKey="Shears, Melanie J" sort="Shears, Melanie J" uniqKey="Shears M" first="Melanie J" last="Shears">Melanie J. Shears</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I</wicri:regionArea><wicri:noRegion>Université Grenoble I</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Botte, Cyrille Y" sort="Botte, Cyrille Y" uniqKey="Botte C" first="Cyrille Y" last="Botté">Cyrille Y. Botté</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I</wicri:regionArea><wicri:noRegion>Université Grenoble I</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I" last="Mcfadden">Geoffrey I. Mcfadden</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia. Electronic address: gim@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="????"><PubDate><MedlineDate>2015 Jan-Feb</MedlineDate></PubDate></date><idno type="RBID">pubmed:25841762</idno><idno type="pmid">25841762</idno><idno type="doi">10.1016/j.molbiopara.2015.03.004</idno><idno type="wicri:Area/PubMed/Corpus">003101</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003101</idno><idno type="wicri:Area/PubMed/Curation">003007</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003007</idno><idno type="wicri:Area/PubMed/Checkpoint">003007</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003007</idno><idno type="wicri:Area/Ncbi/Merge">002415</idno><idno type="wicri:Area/Ncbi/Curation">002415</idno><idno type="wicri:Area/Ncbi/Checkpoint">002415</idno><idno type="wicri:Area/Main/Merge">00F541</idno><idno type="wicri:Area/Main/Curation">00E301</idno><idno type="wicri:Area/Main/Exploration">00E301</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.</title><author><name sortKey="Shears, Melanie J" sort="Shears, Melanie J" uniqKey="Shears M" first="Melanie J" last="Shears">Melanie J. Shears</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I</wicri:regionArea><wicri:noRegion>Université Grenoble I</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Botte, Cyrille Y" sort="Botte, Cyrille Y" uniqKey="Botte C" first="Cyrille Y" last="Botté">Cyrille Y. Botté</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>School of BioSciences, University of Melbourne, Australia; Apicolipid Group, UMR5163, CNRS, Université Grenoble I</wicri:regionArea><wicri:noRegion>Université Grenoble I</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I" last="Mcfadden">Geoffrey I. Mcfadden</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, Australia. Electronic address: gim@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></analytic><series><title level="j">Molecular and biochemical parasitology</title><idno type="eISSN">1872-9428</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antimalarials (isolation & purification)</term><term>Antimalarials (pharmacology)</term><term>Apicoplasts (metabolism)</term><term>Biomedical Research (trends)</term><term>Drug Discovery (trends)</term><term>Fatty Acids (metabolism)</term><term>Malaria Vaccines (immunology)</term><term>Malaria Vaccines (isolation & purification)</term><term>Plasmodium (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides gras (métabolisme)</term><term>Antipaludiques (isolement et purification)</term><term>Antipaludiques (pharmacologie)</term><term>Apicoplastes (métabolisme)</term><term>Découverte de médicament (tendances)</term><term>Plasmodium (métabolisme)</term><term>Recherche biomédicale (tendances)</term><term>Vaccins contre le paludisme (immunologie)</term><term>Vaccins contre le paludisme (isolement et purification)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Malaria Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antimalarials</term><term>Malaria Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Fatty Acids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antimalarials</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Vaccins contre le paludisme</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Antipaludiques</term><term>Vaccins contre le paludisme</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Apicoplasts</term><term>Plasmodium</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acides gras</term><term>Apicoplastes</term><term>Plasmodium</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antipaludiques</term></keywords><keywords scheme="MESH" qualifier="tendances" xml:lang="fr"><term>Découverte de médicament</term><term>Recherche biomédicale</term></keywords><keywords scheme="MESH" qualifier="trends" xml:lang="en"><term>Biomedical Research</term><term>Drug Discovery</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The malaria parasite Plasmodium possesses a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is essential for parasite survival, and harbors several plant-like metabolic pathways including a type II fatty acid synthesis (FASII) pathway. The FASII pathway was discovered in 1998, and much of the early research in the field pursued it as a therapeutic drug target. These studies identified a range of compounds with activity against bloodstage parasites and led to the localization and characterization of most enzymes in the pathway. However, when genetic studies revealed FASII was dispensable in bloodstage parasites, it effectively discounted the pathway as a therapeutic drug target, and suggested these compounds instead interfered with other processes. Interest in FASII then shifted toward its disruption for malaria prophylaxis and vaccine development, with experiments in rodent malaria models identifying a crucial role for the pathway in the parasite's transition from the liver to the blood. Unexpectedly however, the human malaria parasite P. falciparum was recently found to differ from rodent models and require FASII for mosquito stage development. This requirement blocked the production of the FASII-deficient forms that might be used as a genetically attenuated parasite vaccine, suggesting the pathway was also unsuitable as a vaccine target. This review discusses how perception of FASII has changed over time, and presents key findings about each enzyme in the pathway to identify remaining questions and opportunities for malaria control.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Victoria (État)"><name sortKey="Shears, Melanie J" sort="Shears, Melanie J" uniqKey="Shears M" first="Melanie J" last="Shears">Melanie J. Shears</name></region><name sortKey="Botte, Cyrille Y" sort="Botte, Cyrille Y" uniqKey="Botte C" first="Cyrille Y" last="Botté">Cyrille Y. Botté</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I" last="Mcfadden">Geoffrey I. Mcfadden</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 00E301 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 00E301 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:25841762
|texte= Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:25841762" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |