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dc.contributor.authorArtavanis-Tsakonas, Katerinaen
dc.contributor.authorHenrici, Ryanen
dc.contributor.authorSutherland, Colinen
dc.date.accessioned2020-10-19T23:31:14Z
dc.date.available2020-10-19T23:31:14Z
dc.identifier.issn0168-6445
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311694
dc.description.abstractStudies of the susceptibility of Plasmodium falciparum to the artemisinin family of antimalarial drugs two major conclusions. Firstly, we propose a dual-component model of artemisinin tolerance in P. falciparum comprising suppression of artemisinin activation in early ring-stage by reducing endocytic provide a complex picture of partial resistance (tolerance) associated with increased parasite survival in vitro and in vivo. We present an overview of the genetic loci that, in mutant form, can independently elicit parasite tolerance. These encode kelch propeller domain protein PfK13, ubiquitin hydrolase UBP-1, actin filament- organising protein Coronin, also carrying a propeller domain, and the trafficking adaptor subunit AP-2. Detailed studies of these proteins and the functional basis of artemisinin tolerance in blood stage parasites are enabling a new synthesis of our understanding to date. To guide further experimental work, we present haemoglobin capture from host cytosol, coupled with enhancement of cellular healing mechanisms in surviving cells. Secondly, these two independent requirements limit the likelihood of development of complete artemisinin resistance by P. falciparum, favouring deployment of existing drugs in new schedules designed to exploit these biological limits, thus extending the useful life of current combination therapies.
dc.publisherOxford University Press
dc.rightsAll rights reserved
dc.titleArtemisinin susceptibility in the malaria parasite Plasmodium falciparum: propellers, adaptor proteins and the need for cellular healingen
dc.typeArticle
prism.publicationNameFEMS Microbiology Reviewsen
dc.identifier.doi10.17863/CAM.58784
dcterms.dateAccepted2020-10-16en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-10-16en
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/R001642/1)
cam.orpheus.counter60*
rioxxterms.freetoread.startdate2023-10-19


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