Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut

Joel Vega-Rodríguez, Anil K. Ghosh, Stefan M. Kanzok, Rhoel R. Dinglasan, Sibao Wang, Nicholas J. Bongio, Dario E. Kalume, Kazutoyo Miura, Carole A. Long, Akhilesh Pandey, Marcelo Jacobs-Lorena

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number4
DOIs
StatePublished - Jan 28 2014
Externally publishedYes

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Plasmodium
Phosphopyruvate Hydratase
Culicidae
Parasites
Plasmodium berghei
Carrier Proteins
Peptides
Peptide Library
Plasmodium falciparum
Life Cycle Stages
Bacteriophages
Epithelium
Clone Cells
Ligands

ASJC Scopus subject areas

  • General

Cite this

Vega-Rodríguez, J., Ghosh, A. K., Kanzok, S. M., Dinglasan, R. R., Wang, S., Bongio, N. J., ... Jacobs-Lorena, M. (2014). Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut. Proceedings of the National Academy of Sciences of the United States of America, 111(4). https://doi.org/10.1073/pnas.1315517111

Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut. / 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 4, 28.01.2014.

Research output: Contribution to journalArticle

Vega-Rodríguez, J, Ghosh, AK, Kanzok, SM, Dinglasan, RR, Wang, S, Bongio, NJ, Kalume, DE, Miura, K, Long, CA, Pandey, A & Jacobs-Lorena, M 2014, 'Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 4. https://doi.org/10.1073/pnas.1315517111
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. / Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 4.
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