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Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

Zannatul Ferdous, Silke Fuchs, Volker Behrends, Nikolaos Trasanidis, Dina Vlachou, View ORCID ProfileGeorge K. Christophides
doi: https://doi.org/10.1101/2020.06.14.151019
Zannatul Ferdous
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Silke Fuchs
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Volker Behrends
2Department of Surgery and Cancer, Imperial College London, London, United Kingdom
3Health Science Research Centre, University of Roehampton, London, United Kingdom
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Nikolaos Trasanidis
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Dina Vlachou
1Department of Life Sciences, Imperial College London, London, United Kingdom
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George K. Christophides
1Department of Life Sciences, Imperial College London, London, United Kingdom
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  • ORCID record for George K. Christophides
  • For correspondence: g.christophides@imperial.ac.uk
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Abstract

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 15, 2020.
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Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding
Zannatul Ferdous, Silke Fuchs, Volker Behrends, Nikolaos Trasanidis, Dina Vlachou, George K. Christophides
bioRxiv 2020.06.14.151019; doi: https://doi.org/10.1101/2020.06.14.151019
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Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding
Zannatul Ferdous, Silke Fuchs, Volker Behrends, Nikolaos Trasanidis, Dina Vlachou, George K. Christophides
bioRxiv 2020.06.14.151019; doi: https://doi.org/10.1101/2020.06.14.151019

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