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dc.contributor.authorDennis, Adelaideen_US
dc.contributor.authorLehane, Adeleen_US
dc.contributor.authorRidgway, Melanieen_US
dc.contributor.authorHolleran, Johnen_US
dc.contributor.authorKirk, Kiaranen_US
dc.date.accessioned2019-05-29T13:03:26Z
dc.date.available2019-05-29T13:03:26Z
dc.date.issued2018en_US
dc.identifier.issn0066-4804en_US
dc.identifier.doi10.1128/AAC.00087-18en_US
dc.identifier.urihttp://hdl.handle.net/10072/379156
dc.description.abstractFor an increasing number of antimalarial agents identified in high-throughput phenotypic screens, there is evidence that they target PfATP4, a putative Na+ efflux transporter on the plasma membrane of the human malaria parasite Plasmodium falciparum. For several such “PfATP4-associated” compounds, it has been noted that their addition to parasitized erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling of both isolated blood-stage parasites and intact parasitized erythrocytes. The swelling of isolated parasites is dependent on the presence of Na+ in the external environment and may be attributed to the osmotic consequences of Na+ uptake. The swelling of the parasitized erythrocyte results in an increase in its osmotic fragility. Countering cell swelling by increasing the osmolarity of the extracellular medium reduces the antiplasmodial efficacy of PfATP4-associated compounds, consistent with cell swelling playing a role in the antimalarial activity of this class of compounds.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherAmerican Society of Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofpagefrom1en_US
dc.relation.ispartofpageto17en_US
dc.relation.ispartofissue6en_US
dc.relation.ispartofjournalAntimicrobial Agents and Chemotherapyen_US
dc.relation.ispartofvolume62en_US
dc.subject.fieldofresearchMicrobiology not elsewhere classifieden_US
dc.subject.fieldofresearchMicrobiologyen_US
dc.subject.fieldofresearchMedical Microbiologyen_US
dc.subject.fieldofresearchcode060599en_US
dc.subject.fieldofresearchcode0605en_US
dc.subject.fieldofresearchcode1108en_US
dc.titleCell Swelling Induced by the Antimalarial KAE609 (Cipargamin) and Other PfATP4-Associated Antimalarialsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dc.type.codeC - Journal Articlesen_US
dc.description.versionPublisheden_US
gro.rights.copyright© 2018 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.en_US
gro.hasfulltextFull Text
gro.griffith.authorHolleran, John


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