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

• Published in: Science (American Association for the Advancement of Science) Vol. 348; no. 6235; pp. 711 - 714
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 08.05.2015
• Subjects: Animals; CD55 Antigens - genetics; Cell Differentiation - genetics; Cells, Cultured; Erythrocytes - cytology; Erythrocytes - metabolism; Erythrocytes - parasitology; Genetic Testing; Hematopoietic Stem Cells - cytology; Host-Parasite Interactions - genetics; Humans; Hyaluronan Receptors - genetics; Malaria, Falciparum - genetics; Malaria, Falciparum - parasitology; Plasmodium falciparum - pathogenicity; RNA, Small Interfering - genetics
• ISSN: 1095-9203
• DOI: 10.1126/science.aaa3526

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.