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  • Dans, Madeline G.Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Springer Nature,2024
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-227301
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-227301URI
  • https://doi.org/10.1038/s41467-024-49491-8DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Boulet, CoralieBurnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland (author)
  • Watson, Gabrielle M.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Nguyen, WilliamWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Dziekan, Jerzy M.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Evelyn, CindyWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Reaksudsan, KitsanapongWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Mehra, SomyaBurnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia (author)
  • Razook, ZahraBurnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia (author)
  • Geoghegan, Niall D.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Mlodzianoski, Michael J.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Goodman, Christopher DeanSchool of Biosciences, The University of Melbourne, VIC, Parkville, Australia (author)
  • Ling, Dawson B.Burnet Institute, VIC, Melbourne, Australia (author)
  • Jonsdottir, Thorey K.Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden(Swepub:umu)thjo0151 (author)
  • Tong, JoshuaWalter and Eliza Hall Institute, VIC, Parkville, Australia (author)
  • Famodimu, Mufuliat ToyinDepartment of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom (author)
  • Kristan, MojcaWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom (author)
  • Pollard, HarryWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom (author)
  • Stewart, Lindsay B.Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom (author)
  • Brandner-Garrod, LukeWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom (author)
  • Sutherland, Colin J.Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom (author)
  • Delves, Michael J.Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom (author)
  • McFadden, Geoffrey I.School of Biosciences, The University of Melbourne, VIC, Parkville, Australia (author)
  • Barry, Alyssa E.Burnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia (author)
  • Crabb, Brendan S.Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; Monash University, VIC, Melbourne, Australia (author)
  • de Koning-Ward, Tania F.Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia (author)
  • Rogers, Kelly L.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Cowman, Alan F.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Tham, Wai-HongWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Sleebs, Brad E.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Gilson, Paul R.Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia (author)
  • Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, AustraliaBurnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland (creator_code:org_t)

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  • In:Nature Communications: Springer Nature15:12041-1723

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