title: Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei.
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 a sexual 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.
authors.affiliation: Department of Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ UK. o.billker@ic.ac.uk
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.forename: Michael K
authors.initials: MK
authors.lastname: Shaw
authors.forename: Ian W
authors.initials: IW
authors.lastname: Jones
authors.forename: Steven V
authors.initials: SV
authors.lastname: Ley
authors.forename: A Jennifer
authors.initials: AJ
authors.lastname: Mordue
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
mesh_terms: D000818:Animals; D007306:Insecticides / Q000494:pharmacology*; D036701:Limonins / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism
chemical_list: D007306:Insecticides; D036701:Limonins; C010329:azadirachtin