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CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts
Author(s) -
Kariu Tohru,
Ishino Tomoko,
Yano Kazuhiko,
Chinzei Yasuo,
Yuda Masao
Publication year - 2006
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.05024.x
Subject(s) - biology , infectivity , microbiology and biotechnology , plasmodium (life cycle) , plasmodium berghei , cytoplasm , microneme , organelle , virology , cell , parasite hosting , midgut , gliding motility , motility , apicomplexa , immunology , plasmodium falciparum , virus , malaria , genetics , botany , world wide web , computer science , larva
Summary 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.