Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition

Plasmodium falciparum malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers of new malaria cases and deaths have been stable in the last years despite intense efforts for disease elimination, highlighting the need for new approaches to stop diseas...

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Main Authors: Chiamaka V. Ukegbu, George K. Christophides, Dina Vlachou
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2021.634273/full
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author Chiamaka V. Ukegbu
George K. Christophides
George K. Christophides
Dina Vlachou
Dina Vlachou
author_facet Chiamaka V. Ukegbu
George K. Christophides
George K. Christophides
Dina Vlachou
Dina Vlachou
author_sort Chiamaka V. Ukegbu
collection DOAJ
description Plasmodium falciparum malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers of new malaria cases and deaths have been stable in the last years despite intense efforts for disease elimination, highlighting the need for new approaches to stop disease transmission. Further understanding of the parasite transmission biology could provide a framework for the development of such approaches. We phenotypically and functionally characterized three novel genes, PIMMS01, PIMMS57, and PIMMS22, using targeted disruption of their orthologs in the rodent parasite Plasmodium berghei. PIMMS01 and PIMMS57 are specifically and highly expressed in ookinetes, while PIMMS22 transcription starts already in gametocytes and peaks in sporozoites. All three genes show strong phenotypes associated with the ookinete to oocyst transition, as their disruption leads to very low numbers of oocysts and complete abolishment of transmission. PIMMS22 has a secondary essential function in the oocyst. Our results enrich the molecular understanding of the parasite-vector interactions and identify PIMMS01, PIMMS57, and PIMMS22 as new targets of transmission blocking interventions.
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spelling doaj.art-4e7cbd1bb9ad43dc910e5cf3e80579cc2022-12-21T22:22:53ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-03-011110.3389/fcimb.2021.634273634273Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental TransitionChiamaka V. Ukegbu0George K. Christophides1George K. Christophides2Dina Vlachou3Dina Vlachou4Department of Life Sciences, Imperial College London, London, United KingdomDepartment of Life Sciences, Imperial College London, London, United KingdomThe Cyprus Institute, Nicosia, CyprusDepartment of Life Sciences, Imperial College London, London, United KingdomThe Cyprus Institute, Nicosia, CyprusPlasmodium falciparum malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers of new malaria cases and deaths have been stable in the last years despite intense efforts for disease elimination, highlighting the need for new approaches to stop disease transmission. Further understanding of the parasite transmission biology could provide a framework for the development of such approaches. We phenotypically and functionally characterized three novel genes, PIMMS01, PIMMS57, and PIMMS22, using targeted disruption of their orthologs in the rodent parasite Plasmodium berghei. PIMMS01 and PIMMS57 are specifically and highly expressed in ookinetes, while PIMMS22 transcription starts already in gametocytes and peaks in sporozoites. All three genes show strong phenotypes associated with the ookinete to oocyst transition, as their disruption leads to very low numbers of oocysts and complete abolishment of transmission. PIMMS22 has a secondary essential function in the oocyst. Our results enrich the molecular understanding of the parasite-vector interactions and identify PIMMS01, PIMMS57, and PIMMS22 as new targets of transmission blocking interventions.https://www.frontiersin.org/articles/10.3389/fcimb.2021.634273/fullookinete developmentmalaria transmissionookinete to oocyst transitionmosquito midgut invasionPlasmodium sporogonic developmentvector-parasite interactions
spellingShingle Chiamaka V. Ukegbu
George K. Christophides
George K. Christophides
Dina Vlachou
Dina Vlachou
Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
Frontiers in Cellular and Infection Microbiology
ookinete development
malaria transmission
ookinete to oocyst transition
mosquito midgut invasion
Plasmodium sporogonic development
vector-parasite interactions
title Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
title_full Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
title_fullStr Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
title_full_unstemmed Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
title_short Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition
title_sort identification of three novel plasmodium factors involved in ookinete to oocyst developmental transition
topic ookinete development
malaria transmission
ookinete to oocyst transition
mosquito midgut invasion
Plasmodium sporogonic development
vector-parasite interactions
url https://www.frontiersin.org/articles/10.3389/fcimb.2021.634273/full
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