Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut

Plasmodium ookinete invasion of the mosquito midgut is a crucial step of the parasite life cycle but little is known about the molecular mechanisms involved. Previously, a phage display peptide library screen identified SM1, a peptide that binds to the mosquito midgut epithelium and inhibits ookinet...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2014-01, Vol.111 (4), p.E492-E500
Main Authors: Vega-Rodríguez, Joel, Ghosh, Anil K, Kanzok, Stefan M, Dinglasan, Rhoel R, Wang, Sibao, Bongio, Nicholas J, Kalume, Dario E, Miura, Kazutoyo, Long, Carole A, Pandey, Akhilesh, Jacobs-Lorena, Marcelo
Format: Article
Language:English
Subjects:
Abdomen - parasitology
Animals
Biological Sciences
Culicidae
Culicidae - parasitology
Malaria
Microbiology
Molecular biology
Parasitic protozoa
Plasmodium berghei
Plasmodium berghei - physiology
Plasmodium falciparum
Plasmodium falciparum - physiology
PNAS Plus
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Summary:Plasmodium ookinete invasion of the mosquito midgut is a crucial step of the parasite life cycle but little is known about the molecular mechanisms involved. Previously, a phage display peptide library screen identified SM1, a peptide that binds to the mosquito midgut epithelium and inhibits ookinete invasion. SM1 was characterized as a mimotope of an ookinete surface enolase and SM1 presumably competes with enolase, the presumed ligand, for binding to a putative midgut receptor. Here we identify a mosquito midgut receptor that binds both SM1 and ookinete surface enolase, termed “enolase-binding protein” (EBP). Moreover, we determined that Plasmodium berghei parasites are heterogeneous for midgut invasion, as some parasite clones are strongly inhibited by SM1 whereas others are not. The SM1-sensitive parasites required the mosquito EBP receptor for midgut invasion whereas the SM1-resistant parasites invaded the mosquito midgut independently of EBP. These experiments provide evidence that Plasmodium ookinetes can invade the mosquito midgut by alternate pathways. Furthermore, another peptide from the original phage display screen, midgut peptide 2 (MP2), strongly inhibited midgut invasion by P. berghei (SM1-sensitive and SM1-resistant) and Plasmodium falciparum ookinetes, suggesting that MP2 binds to a separate, universal receptor for midgut invasion.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1315517111