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

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

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

Author(s) -

Elizabeth S. Egan,

Rays H. Y. Jiang,

Mischka A. Moechtar,

Natasha S. Barteneva,

Michael P. Weekes,

Luís Nobre,

Steven P. Gygi,

João A. Paulo,

Charles Frantzreb,

Yoshihiko Tani,

Junko Takahashi,

Seishi Watanabe,

Jonathan M. Goldberg,

Aditya S. Paul,

Carlo Brugnara,

David E. Root,

Roger C. Wiegand,

John G. Doench,

Manoj T. Duraisingh

Publication year - 2015

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aaa3526

Subject(s) - plasmodium falciparum , biology , malaria , haematopoiesis , genetic screen , host (biology) , host factors , hematopoietic stem cell , red blood cell , microbiology and biotechnology , immunology , stem cell , genetics , gene , phenotype , virus

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.

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