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Plasmodium DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.

ABSTRACT: Cells use fatty acids (FAs) for membrane biosynthesis, energy storage, and the generation of signaling molecules. 3-hydroxyacyl-CoA dehydratase-DEH-is a key component of very long chain fatty acid synthesis. Here, we further characterized in-depth the location and function of DEH, applying in silico analysis, live cell imaging, reverse genetics, and ultrastructure analysis using the mouse malaria model Plasmodium berghei DEH is evolutionarily conserved across eukaryotes, with a single DEH in Plasmodium spp. and up to three orthologs in the other eukaryotes studied. DEH-GFP live-cell imaging showed strong GFP fluorescence throughout the life-cycle, with areas of localized expression in the cytoplasm and a circular ring pattern around the nucleus that colocalized with ER markers. ?deh mutants showed a small but significant reduction in oocyst size compared with WT controls from day 10 postinfection onwards, and endomitotic cell division and sporogony were completely ablated, blocking parasite transmission from mosquito to vertebrate host. Ultrastructure analysis confirmed degeneration of ?deh oocysts, and a complete lack of sporozoite budding. Overall, DEH is evolutionarily conserved, localizes to the ER, and plays a crucial role in sporogony.

SUBMITTER: Guttery DS

PROVIDER: S-EPMC7652392 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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<i>Plasmodium</i> DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.

Guttery David S DS Pandey Rajan R Ferguson David Jp DJ Wall Richard J RJ Brady Declan D Gupta Dinesh D Holder Anthony A AA Tewari Rita R

Life science alliance 20201026 12

Cells use fatty acids (FAs) for membrane biosynthesis, energy storage, and the generation of signaling molecules. 3-hydroxyacyl-CoA dehydratase-DEH-is a key component of very long chain fatty acid synthesis. Here, we further characterized in-depth the location and function of DEH, applying in silico analysis, live cell imaging, reverse genetics, and ultrastructure analysis using the mouse malaria model <i>Plasmodium berghei</i> DEH is evolutionarily conserved across eukaryotes, with a single DEH ...[more]

PMID: 33106323

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Project description:BACKGROUND: The control of most vectors of malaria is threatened by the spread of insecticide resistance. One factor that has been hitherto largely overlooked is the potential effects of insecticide resistance on the ability of mosquitoes to transmit malaria: are insecticide-resistant mosquitoes as good vectors of Plasmodium as susceptible ones? The drastic physiological changes that accompany the evolution of insecticide resistance may indeed alter the ability of vectors to transmit diseases, a possibility that, if confirmed, could have major epidemiological consequences. METHODS: Using a novel experimental system consisting of the avian malaria parasite (Plasmodium relictum) and its natural vector (the mosquito Culex pipiens), two of the most common mechanisms of insecticide resistance (esterase overproduction and acetylcholinesterase modification) were investigated for their effect on mosquito infection rate and parasite burden. For this purpose two types of experiments were carried out using (i) insecticide-resistant and susceptible laboratory isogenic lines of Cx. pipiens and (ii) wild Cx. pipiens collected from a population where insecticide resistant and susceptible mosquitoes coexist in sympatry. RESULTS: The isogenic line and wild-caught mosquito experiments were highly consistent in showing no effect of either esterase overproduction or of acetylcholinesterase modification on either the infection rate or on the oocyst burden of mosquitoes. The only determinant of these traits was blood meal size, which was similar across the different insecticide resistant categories in both experiments. CONCLUSIONS: Insecticide resistance was found to have no effect on Plasmodium development within the mosquito. This is the first time this question has been addressed using a natural mosquito-Plasmodium combination, while taking care to standardize the genetic background against which the insecticide resistance genes operate. Infection rate and oocyst burden are but two of the factors that determine the vectorial capacity of mosquitoes. Other key determinants of parasite transmission, such as mosquito longevity and behaviour, or the parasite's incubation time, need to be investigated before concluding on whether insecticide resistance influences the ability of mosquitoes to transmit malaria.

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Plasmodium DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.

Publications

<i>Plasmodium</i> DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.

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