Azadirachtin Disrupts Formation of Organised Microtubule Arrays during Micogametogenesis of Plasmodium berghei

O. Billker, M. K. Shaw, I. W. Jones, S. V. Ley, Anne Jennifer Mordue, R. E. Sinden

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    Transmission of malaria parasites from vertebrate blood to the mosquito vector depends critically on the differentiation of the gametocytes into gametes. This occurs in response to environmental stimuli encountered by the parasite in the mosquito bloodmeal. Male gametogenesis involves three rounds of DNA replication and endomitosis, and the assembly de novo of 8 motile axonemes. Azadirachtin, a plant limnoid and insecticide with an unkown mode of action, specifically inhibits the release of motile gametes from activated microgametocytes but does not inhibit growth and replication of asexual blood stages. We have combined confocal laser scanning microscopy and transmission electron microscopy to examine the effect of azadirachtin on the complex reorganisation of the microtubule cytoskeleton during gametogenesis in Plasmodium berghei. Neither the replication of the genome nor the ability of tubulin monomers to assemble into microtubules upon gametocyte activation were prevented by azadirachtin. However, the drug interfered with the formation of mitotic spindles and with the assembly of microtubules into typical axonemes. Our observations suggest that azadarachtin specifically disrupts the patterning of microtubules into more complex structures, such as mitotic spindles and axonemes.

    Original languageEnglish
    Pages (from-to)489-497
    Number of pages8
    JournalJournal of Eukaryotic Microbiology
    Volume49
    DOIs
    Publication statusPublished - 2002

    Keywords

    • apicomplexa
    • axoneme
    • Azadirachta indica
    • cytoskeleton
    • gametogenesis
    • mitosis
    • mitotic spindle
    • Plasmodium berghei
    • tubulin
    • ultrastructure
    • SCHISTOCERCA-GREGARIA FORSKAL
    • GAMMA-TUBULIN GENE
    • SPINDLE POLE BODY
    • IN-VITRO
    • SACCHAROMYCES-CEREVISIAE
    • MALARIA PARASITES
    • XANTHURENIC ACID
    • DESERT LOCUST
    • BINDING-SITES
    • ORGANIZATION

    Cite this

    Azadirachtin Disrupts Formation of Organised Microtubule Arrays during Micogametogenesis of Plasmodium berghei. / Billker, O.; Shaw, M. K.; Jones, I. W.; Ley, S. V.; Mordue, Anne Jennifer; Sinden, R. E.

    In: Journal of Eukaryotic Microbiology, Vol. 49, 2002, p. 489-497.

    Research output: Contribution to journalArticle

    Billker, O. ; Shaw, M. K. ; Jones, I. W. ; Ley, S. V. ; Mordue, Anne Jennifer ; Sinden, R. E. / Azadirachtin Disrupts Formation of Organised Microtubule Arrays during Micogametogenesis of Plasmodium berghei. In: Journal of Eukaryotic Microbiology. 2002 ; Vol. 49. pp. 489-497.
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    AB - Transmission of malaria parasites from vertebrate blood to the mosquito vector depends critically on the differentiation of the gametocytes into gametes. This occurs in response to environmental stimuli encountered by the parasite in the mosquito bloodmeal. Male gametogenesis involves three rounds of DNA replication and endomitosis, and the assembly de novo of 8 motile axonemes. Azadirachtin, a plant limnoid and insecticide with an unkown mode of action, specifically inhibits the release of motile gametes from activated microgametocytes but does not inhibit growth and replication of asexual blood stages. We have combined confocal laser scanning microscopy and transmission electron microscopy to examine the effect of azadirachtin on the complex reorganisation of the microtubule cytoskeleton during gametogenesis in Plasmodium berghei. Neither the replication of the genome nor the ability of tubulin monomers to assemble into microtubules upon gametocyte activation were prevented by azadirachtin. However, the drug interfered with the formation of mitotic spindles and with the assembly of microtubules into typical axonemes. Our observations suggest that azadarachtin specifically disrupts the patterning of microtubules into more complex structures, such as mitotic spindles and axonemes.

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