Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    A high-content phenotypic screen reveals the disruptive potency of quinacrine and 3',4'-Dichlorobenzamil on the digestive vacuole of plasmodium falciparum

    Access Status
    Open access via publisher
    Authors
    Lee, Y.
    Goh, A.
    Ch'Ng, J.
    Nosten, F.
    Preiser, P.
    Pervaiz, Shazib
    Yadav, S.
    Tan, K.
    Date
    2014
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Lee, Y. and Goh, A. and Ch'Ng, J. and Nosten, F. and Preiser, P. and Pervaiz, S. and Yadav, S. et al. 2014. A high-content phenotypic screen reveals the disruptive potency of quinacrine and 3',4'-Dichlorobenzamil on the digestive vacuole of plasmodium falciparum. Antimicrobial Agents and Chemotherapy. 58 (1): pp. 550-558.
    Source Title
    Antimicrobial Agents and Chemotherapy
    DOI
    10.1128/AAC.01441-13
    ISSN
    0066-4804
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/51046
    Collection
    • Curtin Research Publications
    Abstract

    Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca2+. This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3',4'-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs. © 2014, American Society for Microbiology.

    Related items

    Showing items related by title, author, creator and subject.

    • Subcellular tracking reveals the location of dimethylsulfoniopropionate in microalgae and visualises its uptake by marine bacteria
      Raina, J.; Clode, P.; Cheong, S.; Bougoure, J.; Kilburn, M.; Reeder, A.; Forêt, S.; Stat, Michael; Beltran, V.; Thomas-Hall, P.; Tapiolas, D.; Motti, C.; Gong, B.; Pernice, M.; Marjo, C.; Seymour, J.; Willis, B.; Bourne, D. (2017)
      © Raina et al.Phytoplankton-bacteria interactions drive the surface ocean sulfur cycle and local climatic processes through the production and exchange of a key compound: dimethylsulfoniopropionate (DMSP). Despite their ...
    • Malodorous dimethylpolysulfides in Perth drinking water.
      Heitz, Anna (2002)
      The formation of an objectionable "swampy" odour in drinking water distribution systems in Perth, Western Australia, was first described by Wajon and co-authors in the mid-1980s (Wajon et al., 1985; Wajon et al., 1986; ...
    • The effect of germination and food processing on the concentration and activity of bioactive compounds in Australian Sweet Lupin
      Rumiyati (2010)
      Lupin is a grain legume which is high in protein and fibre, but low in fat and starch. Lupin also contains bioactive compounds such as phenolic compounds. Many studies have shown that a diet containing lupin has health ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.