Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination
Plasmodium parasites have a complex life cycle that includes development in the human host as well as the Anopheles vector. Successful transmission of the parasite between its host and vector therefore requires the parasite to balance its investments in asexual replication and sexual reproduction, v...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.901971/full |
| _version_ | 1818163992337580032 |
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| author | Mariëtte E. van der Watt Janette Reader Janette Reader Lyn-Marié Birkholtz Lyn-Marié Birkholtz |
| author_facet | Mariëtte E. van der Watt Janette Reader Janette Reader Lyn-Marié Birkholtz Lyn-Marié Birkholtz |
| author_sort | Mariëtte E. van der Watt |
| collection | DOAJ |
| description | Plasmodium parasites have a complex life cycle that includes development in the human host as well as the Anopheles vector. Successful transmission of the parasite between its host and vector therefore requires the parasite to balance its investments in asexual replication and sexual reproduction, varying the frequency of sexual commitment to persist within the human host and generate future opportunities for transmission. The transmission window is extended further by the ability of stage V gametocytes to circulate in peripheral blood for weeks, whereas immature stage I to IV gametocytes sequester in the bone marrow and spleen until final maturation. Due to the low gametocyte numbers in blood circulation and with the ease of targeting such life cycle bottlenecks, transmission represents an efficient target for therapeutic intervention. The biological process of Plasmodium transmission is a multistage, multifaceted process and the past decade has seen a much deeper understanding of the molecular mechanisms and regulators involved. Clearly, specific and divergent processes are used during transmission compared to asexual proliferation, which both poses challenges but also opportunities for discovery of transmission-blocking antimalarials. This review therefore presents an update of our molecular understanding of gametocyte and gamete biology as well as the status of transmission-blocking activities of current antimalarials and lead development compounds. By defining the biological components associated with transmission, considerations for the development of new transmission-blocking drugs to target such untapped but unique biology is suggested as an important, main driver for transmission-blocking drug discovery. |
| first_indexed | 2024-12-11T16:58:22Z |
| format | Article |
| id | doaj.art-e64b74d5a9a149beb99bb32738761d83 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-11T16:58:22Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-e64b74d5a9a149beb99bb32738761d832022-12-22T00:57:54ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-06-011210.3389/fcimb.2022.901971901971Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria EliminationMariëtte E. van der Watt0Janette Reader1Janette Reader2Lyn-Marié Birkholtz3Lyn-Marié Birkholtz4Institute for Sustainable Malaria Control, School of Health Systems and Public Health, University of Pretoria, Pretoria, South AfricaInstitute for Sustainable Malaria Control, School of Health Systems and Public Health, University of Pretoria, Pretoria, South AfricaDepartment of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South AfricaInstitute for Sustainable Malaria Control, School of Health Systems and Public Health, University of Pretoria, Pretoria, South AfricaDepartment of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South AfricaPlasmodium parasites have a complex life cycle that includes development in the human host as well as the Anopheles vector. Successful transmission of the parasite between its host and vector therefore requires the parasite to balance its investments in asexual replication and sexual reproduction, varying the frequency of sexual commitment to persist within the human host and generate future opportunities for transmission. The transmission window is extended further by the ability of stage V gametocytes to circulate in peripheral blood for weeks, whereas immature stage I to IV gametocytes sequester in the bone marrow and spleen until final maturation. Due to the low gametocyte numbers in blood circulation and with the ease of targeting such life cycle bottlenecks, transmission represents an efficient target for therapeutic intervention. The biological process of Plasmodium transmission is a multistage, multifaceted process and the past decade has seen a much deeper understanding of the molecular mechanisms and regulators involved. Clearly, specific and divergent processes are used during transmission compared to asexual proliferation, which both poses challenges but also opportunities for discovery of transmission-blocking antimalarials. This review therefore presents an update of our molecular understanding of gametocyte and gamete biology as well as the status of transmission-blocking activities of current antimalarials and lead development compounds. By defining the biological components associated with transmission, considerations for the development of new transmission-blocking drugs to target such untapped but unique biology is suggested as an important, main driver for transmission-blocking drug discovery.https://www.frontiersin.org/articles/10.3389/fcimb.2022.901971/fullantimalarialsgametegametocytemalariaPlasmodiumsexual commitment |
| spellingShingle | Mariëtte E. van der Watt Janette Reader Janette Reader Lyn-Marié Birkholtz Lyn-Marié Birkholtz Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination Frontiers in Cellular and Infection Microbiology antimalarials gamete gametocyte malaria Plasmodium sexual commitment |
| title | Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination |
| title_full | Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination |
| title_fullStr | Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination |
| title_full_unstemmed | Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination |
| title_short | Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination |
| title_sort | adapt or die targeting unique transmission stage biology for malaria elimination |
| topic | antimalarials gamete gametocyte malaria Plasmodium sexual commitment |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.901971/full |
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