CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts.
The malarial parasite has two hosts in its life cycle, a vertebrate and a mosquito. We report here that malarial invasion into these hosts is mediated by a protein, designated cell-traversal protein for ookinetes and sporozoites (CelTOS), which is localized to micronemes that are organelles for parasite invasive motility. Targeted disruption of the CelTOS gene in Plasmodium berghei reduced parasite infectivity in the mosquito host approximately 200-fold. The disruption also reduced the sporozoite infectivity in the liver and almost abolished its cell-passage ability. Liver infectivity was restored in Kupffer cell-depleted rats, indicating that CelTOS is necessary for sporozoite passage from the circulatory system to hepatocytes through the liver sinusoidal cell layer. Electron microscopic analysis revealed that celtos-disrupted ookinetes invade the midgut epithelial cell by rupturing the cell membrane, but then fail to cross the cell, indicating that CelTOS is necessary for migration through the cytoplasm. These results suggest that conserved cell-passage mechanisms are used by both sporozoites and ookinetes to breach host cellular barriers. Elucidation of these mechanisms might lead to novel antimalarial strategies to block parasite's transmission.
Kariu
Tohru
T
Mie University, School of Medicine, 2-174 Edobashi, Tsu, Mie 514-0001, Japan.
Ishino
Tomoko
T
Yano
Kazuhiko
K
Chinzei
Yasuo
Y
Yuda
Masao
M
D000595:Amino Acid Sequence; D000818:Animals; D009033:Culicidae / Q000469:parasitology*; D020224:Expressed Sequence Tags; D041981:Gastrointestinal Tract / Q000166:cytology / Q000469:parasitology; D006790:Host-Parasite Interactions; D007303:Insect Vectors; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000235:genetics / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D033761:Spores, Protozoan / Q000378:metabolism
C509909:CelTOS protein, Plasmodium berghei; D015800:Protozoan Proteins