Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis.
A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously discovered through the observation that all progeny clones in a Dd2 x HB3 genetic cross were the result of fertilization events between Dd2 female and HB3 male gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an 800-kb segment on chromosome 12. Here, we report further mapping of the determinant to an 82-kb region and the identification of a candidate gene, P. falciparum male development gene 1 (pfmdv-1), that is expressed at a lower level in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2. Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma membrane, parasitophorous vacuole membrane, and the membranes of cleft-like structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic reduction in mature gametocytes, especially functional male gametocytes, with the majority of sexually committed parasites developmentally arrested at stage I. The pfmdv-1-knockout parasites show disturbed membrane structures, particularly multimembrane vesicles/tubes that likely derive from deformed cleft-like structures. Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity.
Furuya
Tetsuya
T
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
Mu
Jianbing
J
Hayton
Karen
K
Liu
Anna
A
Duan
Junhui
J
Nkrumah
Louis
L
Joy
Deirdre A
DA
Fidock
David A
DA
Fujioka
Hisashi
H
Vaidya
Akhil B
AB
Wellems
Thomas E
TE
Su
Xin-zhuan
XZ
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D005854:Germ Cells / Q000166:cytology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development*; D020133:Reverse Transcriptase Polymerase Chain Reaction