Essential role of membrane-attack protein in malarial transmission to mosquito host.
نویسندگان
چکیده
After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. Here we report that a microneme protein with a membrane-attack complex and perforin (MACPF)-related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs.
منابع مشابه
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 para...
متن کاملMAEBL Is Essential for Malarial Sporozoite Infection of the Mosquito Salivary Gland
Malarial sporozoites mature in the oocysts formed in the mosquito midgut wall and then selectively invade the salivary glands, where they wait to be transmitted to the vertebrate host via mosquito bite. Invasion into the salivary gland has been thought to be mediated by specific ligand-receptor interactions, but the molecules involved in these interactions remain unknown. MAEBL is a single tran...
متن کاملRole of mosquito salivary glands
This review briefly focuses on the role of mosquito salivary glands; and on the biological processes and mechanisms relevant to transmission of malarial parasite (Plasmodium), the causative agent for malaria. A key requirement for transmission of the parasite is an infected blood meal which initiates parasite transmission cycle. The blood feeding is an organized biological mechanism which invol...
متن کاملInfectivity of malarial parasites to mosquitoes: 'the interdependent roles of parasite, vector and host'.
It has been possible to infect mosquitoes routinely with cultured gametocytes of Plasmodium falciparum since 1980. This has enabled the development of a reliable bio-assay for potential transmission-blocking vaccines and research on the role of specific antibodies from the host on the parasitic stages in the mosquito midgut. After some development and fine-tuning of the assay, it became apparen...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 101 46 شماره
صفحات -
تاریخ انتشار 2004