Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against <i>Plasmodium</i> parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with <i>Plasmodium ber...

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Main Authors: Elena Lantero, Jessica Fernandes, Carlos Raúl Aláez-Versón, Joana Gomes, Henrique Silveira, Fatima Nogueira, Xavier Fernàndez-Busquets
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/10/8/1136
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author Elena Lantero
Jessica Fernandes
Carlos Raúl Aláez-Versón
Joana Gomes
Henrique Silveira
Fatima Nogueira
Xavier Fernàndez-Busquets
author_facet Elena Lantero
Jessica Fernandes
Carlos Raúl Aláez-Versón
Joana Gomes
Henrique Silveira
Fatima Nogueira
Xavier Fernàndez-Busquets
author_sort Elena Lantero
collection DOAJ
description Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against <i>Plasmodium</i> parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with <i>Plasmodium berghei</i>-infected blood to <i>Anopheles stephensi</i> mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite’s ookinete–oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.
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spelling doaj.art-e649f085d3544929a5f6f838f85ef5c62023-11-20T08:46:17ZengMDPI AGBiomolecules2218-273X2020-08-01108113610.3390/biom10081136Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the MosquitoElena Lantero0Jessica Fernandes1Carlos Raúl Aláez-Versón2Joana Gomes3Henrique Silveira4Fatima Nogueira5Xavier Fernàndez-Busquets6Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10–12, ES-08028 Barcelona, SpainGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, PortugalBIOIBERICA S.A.U., Polígon Industrial “Mas Puigvert”, Ctra. N-II, km. 680.6, ES-08389 Palafolls, SpainGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, PortugalGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, PortugalGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, PortugalInstitute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10–12, ES-08028 Barcelona, SpainInnovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against <i>Plasmodium</i> parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with <i>Plasmodium berghei</i>-infected blood to <i>Anopheles stephensi</i> mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite’s ookinete–oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.https://www.mdpi.com/2218-273X/10/8/1136malariaheparinmosquito<i>Plasmodium</i><i>Anopheles</i>ookinete
spellingShingle Elena Lantero
Jessica Fernandes
Carlos Raúl Aláez-Versón
Joana Gomes
Henrique Silveira
Fatima Nogueira
Xavier Fernàndez-Busquets
Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
Biomolecules
malaria
heparin
mosquito
<i>Plasmodium</i>
<i>Anopheles</i>
ookinete
title Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
title_full Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
title_fullStr Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
title_full_unstemmed Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
title_short Heparin Administered to <i>Anopheles</i> in Membrane Feeding Assays Blocks <i>Plasmodium</i> Development in the Mosquito
title_sort heparin administered to i anopheles i in membrane feeding assays blocks i plasmodium i development in the mosquito
topic malaria
heparin
mosquito
<i>Plasmodium</i>
<i>Anopheles</i>
ookinete
url https://www.mdpi.com/2218-273X/10/8/1136
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