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Tadalafil impacts the mechanical properties of Plasmodium falciparum gametocyte-infected erythrocytes.
- Source :
-
Molecular and biochemical parasitology [Mol Biochem Parasitol] 2021 Jul; Vol. 244, pp. 111392. Date of Electronic Publication: 2021 Jun 23. - Publication Year :
- 2021
-
Abstract
- Plasmodium falciparum gametocytes modify the mechanical properties of their erythrocyte host to persist for several weeks in the blood circulation and to be available for mosquitoes. These changes are tightly regulated by the plasmodial phosphodiesterase delta that decreases both the stiffness and the permeability of the infected host cell. Here, we address the effect of the phosphodiesterase inhibitor tadalafil on deformability and permeability of gametocyte-infected erythrocytes. We show that this inhibitor drastically increases isosmotic lysis of gametocyte-infected erythrocytes and impairs their ability to circulate in an in vitro model for splenic retention. These findings indicate that tadalafil represents a novel drug lead potentially capable of blocking malaria parasite transmission by impacting gametocyte circulation.<br /> (Copyright © 2021. Published by Elsevier B.V.)
- Subjects :
- Biomechanical Phenomena
Cell Membrane Permeability drug effects
Cyclic Nucleotide Phosphodiesterases, Type 5 metabolism
Erythrocyte Deformability drug effects
Erythrocytes drug effects
Erythrocytes parasitology
Erythrocytes ultrastructure
Female
Gene Expression
Host-Parasite Interactions drug effects
Host-Parasite Interactions genetics
Humans
Life Cycle Stages genetics
Male
Plasmodium falciparum enzymology
Plasmodium falciparum genetics
Plasmodium falciparum growth & development
Protozoan Proteins genetics
Protozoan Proteins metabolism
Reproduction, Asexual drug effects
Cyclic Nucleotide Phosphodiesterases, Type 5 genetics
Gametogenesis drug effects
Life Cycle Stages drug effects
Phosphodiesterase 5 Inhibitors pharmacology
Plasmodium falciparum drug effects
Protozoan Proteins antagonists & inhibitors
Tadalafil pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9428
- Volume :
- 244
- Database :
- MEDLINE
- Journal :
- Molecular and biochemical parasitology
- Publication Type :
- Academic Journal
- Accession number :
- 34171456
- Full Text :
- https://doi.org/10.1016/j.molbiopara.2021.111392