A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion

Elizabeth S. Egan, Rays H Y Jiang, Mischka A. Moechtar, Natasha S. Barteneva, Michael P. Weekes, Luis V. Nobre, Steven P. Gygi, Joao A. Paulo, Charles Frantzreb, Yoshihiko Tani, Junko Takahashi, Seishi Watanabe, Jonathan Goldberg, Aditya S. Paul, Carlo Brugnara, David E. Root, Roger C. Wiegand, John G. Doench, Manoj T. Duraisingh

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.

Original languageEnglish
Pages (from-to)711-714
Number of pages4
JournalScience
Volume348
Issue number6235
DOIs
Publication statusPublished - May 8 2015
Externally publishedYes

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Plasmodium falciparum
Erythrocytes
Malaria
Hematopoietic Stem Cells
Parasites
Therapeutics

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Egan, E. S., Jiang, R. H. Y., Moechtar, M. A., Barteneva, N. S., Weekes, M. P., Nobre, L. V., ... Duraisingh, M. T. (2015). A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion. Science, 348(6235), 711-714. https://doi.org/10.1126/science.aaa3526

A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion. / Egan, Elizabeth S.; Jiang, Rays H Y; Moechtar, Mischka A.; Barteneva, Natasha S.; Weekes, Michael P.; Nobre, Luis V.; Gygi, Steven P.; Paulo, Joao A.; Frantzreb, Charles; Tani, Yoshihiko; Takahashi, Junko; Watanabe, Seishi; Goldberg, Jonathan; Paul, Aditya S.; Brugnara, Carlo; Root, David E.; Wiegand, Roger C.; Doench, John G.; Duraisingh, Manoj T.

In: Science, Vol. 348, No. 6235, 08.05.2015, p. 711-714.

Research output: Contribution to journalArticle

Egan, ES, Jiang, RHY, Moechtar, MA, Barteneva, NS, Weekes, MP, Nobre, LV, Gygi, SP, Paulo, JA, Frantzreb, C, Tani, Y, Takahashi, J, Watanabe, S, Goldberg, J, Paul, AS, Brugnara, C, Root, DE, Wiegand, RC, Doench, JG & Duraisingh, MT 2015, 'A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion', Science, vol. 348, no. 6235, pp. 711-714. https://doi.org/10.1126/science.aaa3526
Egan, Elizabeth S. ; Jiang, Rays H Y ; Moechtar, Mischka A. ; Barteneva, Natasha S. ; Weekes, Michael P. ; Nobre, Luis V. ; Gygi, Steven P. ; Paulo, Joao A. ; Frantzreb, Charles ; Tani, Yoshihiko ; Takahashi, Junko ; Watanabe, Seishi ; Goldberg, Jonathan ; Paul, Aditya S. ; Brugnara, Carlo ; Root, David E. ; Wiegand, Roger C. ; Doench, John G. ; Duraisingh, Manoj T. / A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion. In: Science. 2015 ; Vol. 348, No. 6235. pp. 711-714.
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