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dc.contributor.authorHapuarachchi, SV
dc.contributor.authorCobbold, SA
dc.contributor.authorShafik, SH
dc.contributor.authorDennis, ASM
dc.contributor.authorMcConville, MJ
dc.contributor.authorMartin, RE
dc.contributor.authorKirk, K
dc.contributor.authorLehane, AM
dc.date.accessioned2020-12-22T03:33:44Z
dc.date.available2020-12-22T03:33:44Z
dc.date.issued2017-02-01
dc.identifierpii: PPATHOGENS-D-16-02056
dc.identifier.citationHapuarachchi, S. V., Cobbold, S. A., Shafik, S. H., Dennis, A. S. M., McConville, M. J., Martin, R. E., Kirk, K. & Lehane, A. M. (2017). The Malaria Parasite's Lactate Transporter PfFNT Is the Target of Antiplasmodial Compounds Identified in Whole Cell Phenotypic Screens. PLOS PATHOGENS, 13 (2), https://doi.org/10.1371/journal.ppat.1006180.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/257880
dc.description.abstractIn this study the 'Malaria Box' chemical library comprising 400 compounds with antiplasmodial activity was screened for compounds that perturb the internal pH of the malaria parasite, Plasmodium falciparum. Fifteen compounds induced an acidification of the parasite cytosol. Two of these did so by inhibiting the parasite's formate nitrite transporter (PfFNT), which mediates the H+-coupled efflux from the parasite of lactate generated by glycolysis. Both compounds were shown to inhibit lactate transport across the parasite plasma membrane, and the transport of lactate by PfFNT expressed in Xenopus laevis oocytes. PfFNT inhibition caused accumulation of lactate in parasitised erythrocytes, and swelling of both the parasite and parasitised erythrocyte. Long-term exposure of parasites to one of the inhibitors gave rise to resistant parasites with a mutant form of PfFNT that showed reduced inhibitor sensitivity. This study provides the first evidence that PfFNT is a druggable antimalarial target.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleThe Malaria Parasite's Lactate Transporter PfFNT Is the Target of Antiplasmodial Compounds Identified in Whole Cell Phenotypic Screens
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1006180
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titlePLoS Pathogens
melbourne.source.volume13
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1180443
melbourne.contributor.authorCobbold, Simon
melbourne.contributor.authorMcConville, Malcolm
dc.identifier.eissn1553-7374
melbourne.accessrightsOpen Access


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