Plasmodium protein kinase 2 is required for ookinete-to-oocyst transition and parasite transmission
6 affiliations
- 1School of Life Sciences, University of Nottingham
- 2Department of Biological Sciences, University of Oxford Brookes
- 3Department of Life Sciences, Imperial College London
- 4Proteomics Core Facility, Faculty of Medicine, University of Geneva
- 5Malaria Parasitology Laboratory, The Francis Crick Institute, London, UK
- 6National Institute of Immunology, New Delhi, India
Abstract
Plasmodium parasites rely on diverse protein kinases to regulate critical processes, yet many remain uncharacterised. Protein kinase 2 (PK2) is required for asexual blood-stage proliferation and merozoite invasion, but its role in sexual stages and transmission is unknown. Here, using live-cell and super-resolution imaging, ultrastructural analysis, functional phenotyping, and quantitative phosphoproteomics, we define the role of PK2 in Plasmodium berghei transmission. PK2 was expressed in merozoites, ookinetes, and sporozoites: the three invasive forms of the parasite. Conditional depletion of PK2 impaired ookinete motility, disrupted apical microneme positioning, abolished oocyst formation, and prevented mosquito-to-host transmission. Direct haemocoel injection of mutant ookinetes failed to restore sporozoite production, demonstrating an additional requirement for PK2 downstream of midgut traversal. Although global protein abundance was largely preserved, phosphoproteomic profiling identified altered phosphorylation of proteins associated with cytoskeletal organisation, host–cell interaction, midgut invasion, and gene regulation. These findings highlight PK2’s critical role across multiple invasive stages, advancing understanding of malaria parasite transmission and identifying putative PK2-regulated pathways as potential targets for transmission-blocking interventions.
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BibTeX
@article{pashley2026plasmodium,
title = {{Plasmodium protein kinase 2 is required for ookinete-to-oocyst transition and parasite transmission}},
author = {Sarah L Pashley and Molly Hair and Chiamaka V Ukegbu and Mohammad Zeeshan and Akancha Mishra and Declan Brady and Robert Markus and Sue Vaughan and Carla Pasquarello and Anthony A Holder and Alexandre Hainard and George K Christophides and Dina Vlachou and Pushkar Sharma and David S Guttery and Rita Tewari},
journal = {Life Science Alliance},
year = {2026},
month = oct,
doi = {10.26508/lsa.202603863},
url = {https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202603863},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Plasmodium protein kinase 2 is required for ookinete-to-oocyst transition and parasite transmission
AU - Sarah L Pashley
AU - Molly Hair
AU - Chiamaka V Ukegbu
AU - Mohammad Zeeshan
AU - Akancha Mishra
AU - Declan Brady
AU - Robert Markus
AU - Sue Vaughan
AU - Carla Pasquarello
AU - Anthony A Holder
AU - Alexandre Hainard
AU - George K Christophides
AU - Dina Vlachou
AU - Pushkar Sharma
AU - David S Guttery
AU - Rita Tewari
PY - 2026
DA - 2026/10/07
JO - Life Science Alliance
DO - 10.26508/lsa.202603863
UR - https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202603863
AB - Plasmodium parasites rely on diverse protein kinases to regulate critical processes, yet many remain uncharacterised. Protein kinase 2 (PK2) is required for asexual blood-stage proliferation and merozoite invasion, but its role in sexual stages and transmission is unknown. Here, using live-cell and super-resolution imaging, ultrastructural analysis, functional phenotyping, and quantitative phosphoproteomics, we define the role of PK2 in Plasmodium berghei transmission. PK2 was expressed in merozoites, ookinetes, and sporozoites: the three invasive forms of the parasite. Conditional depletion of PK2 impaired ookinete motility, disrupted apical microneme positioning, abolished oocyst formation, and prevented mosquito-to-host transmission. Direct haemocoel injection of mutant ookinetes failed to restore sporozoite production, demonstrating an additional requirement for PK2 downstream of midgut traversal. Although global protein abundance was largely preserved, phosphoproteomic profiling identified altered phosphorylation of proteins associated with cytoskeletal organisation, host–cell interaction, midgut invasion, and gene regulation. These findings highlight PK2’s critical role across multiple invasive stages, advancing understanding of malaria parasite transmission and identifying putative PK2-regulated pathways as potential targets for transmission-blocking interventions.
SN - 2575-1077
ER -