Imperial College London
Alternate

Dr Dina Vlachou

Faculty of Natural Sciences, Department of Life Sciences

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 1267d.vlachou Website

 
 
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Location

 

612Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bailey:2023:10.1073/pnas.2304339120,
author = {Bailey, AJ and Ukegbu, CV and Giorgalli, M and Besson, TRB and Christophides, GK and Vlachou, D},
doi = {10.1073/pnas.2304339120},
journal = {Proc Natl Acad Sci U S A},
title = {Intracellular Plasmodium aquaporin 2 is important for sporozoite production in the mosquito vector and malaria transmission.},
url = {http://dx.doi.org/10.1073/pnas.2304339120},
volume = {120},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Malaria remains a devastating disease and, with current measures failing to control its transmission, there is a need for novel interventions. A family of proteins that have long been pursued as potential intervention targets are aquaporins, which are channels facilitating the movement of water and other solutes across membranes. We identify an aquaporin in malaria parasites and demonstrate that it is important for completion of Plasmodium development in the mosquito vector. Disruption of AQP2 in the human parasite Plasmodium falciparum and the rodent parasite Plasmodium berghei blocks sporozoite production inside oocysts established on mosquito midguts, greatly limiting parasite infection of salivary glands and transmission to a new host. In vivo epitope tagging of AQP2 in P. berghei, combined with immunofluorescence assays, reveals that the protein is localized in vesicle-like organelles found in the cytoplasm of gametocytes, ookinetes, and sporozoites. The number of these organelles varies between individual parasites and lifecycle stages suggesting that they are likely part of a dynamic endomembrane system. Phylogenetic analysis confirms that AQP2 is unique to malaria and closely related parasites and most closely resembles intracellular aquaporins. Structure prediction analyses identify several unusual features, including a large accessory extracellular loop and an arginine-to-phenylalanine substitution in the selectivity filter principally determining pore function, a unique feature among known aquaporins. This in conjunction with the importance of AQP2 for malaria transmission suggests that AQP2 may be a fruitful target of antimalarial interventions.
AU  - Bailey,AJ
AU  - Ukegbu,CV
AU  - Giorgalli,M
AU  - Besson,TRB
AU  - Christophides,GK
AU  - Vlachou,D
DO  - 10.1073/pnas.2304339120
PY  - 2023///
TI  - Intracellular Plasmodium aquaporin 2 is important for sporozoite production in the mosquito vector and malaria transmission.
T2  - Proc Natl Acad Sci U S A
UR  - http://dx.doi.org/10.1073/pnas.2304339120
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37883438
VL  - 120
ER  -
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