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

作者: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*
来源:Science, 2015, 348(6235): 711-714.
DOI:10.1126/science.aaa3526

摘要

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.