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Title: GLIDING MOTILITY LEADS TO ACTIVE CELLULAR INVASION BY CRYPTOSPORIDIUM SPOROZOITES

Author
item WETZEL, DAWN - ST. LOUIS, MO
item SCHMIDT, JOANN - URBANA, IL
item KUHLENSCHMIDT, MARK - URBANA, IL
item Dubey, Jitender
item SIBLEY, DAVID - ST. LOUIS, MO

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2005
Publication Date: 12/12/2005
Citation: Wetzel, D.M., Schmidt, J., Kuhlenschmidt, M.S., Dubey, J.P., Sibley, D. 2005. Gliding motility leads to active cellular invasion by cryptosporidium sporozoites. Infection and Immunity. 73:5379-5387.

Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide. It causes mental retardation and loss of vision in children, and abortion in livestock. Cats are the main reservoir of T. gondii because they are the only hosts that can excrete the resistant stage (oocyst) of the parasite in the feces. Humans become infected by eating undercooked meat from infected animals and food and water contaminated with oocysts. Scientists at the Beltsville Agricultural Research Center and Washington Medical School, Missouri compare motility patterns in different stages of Toxoplasma sporozoites and tachyzoites with sporozoites of the related coccidium, Cryptosporodium. The results will be of interest to biologists, parasitologists, and veterinarians.

Technical Abstract: We examined gliding motility and cell invasion by an early branching apicomplexan, Cryptosporidium parvum, which causes diarrheal disease in humans and animals. Real-time video microscopy demonstrated that C. parvum sporozoites undergo circular and helical gliding, two of the three stereotypical movements exhibited by Toxoplasma gondii tachyzoites. C. parvum sporozoites moved more rapidly than T. gondii sporozoites, which showed the same rates of motility as tachyzoites. Motility by C. parvum sporozoites was prevented by latrunculin B and cytochalasin D, drugs that depolymerize the parasite actin cytoskeleton, and by the myosin inhibitor 2,3-butanedione monoxime. Imaging of the initial events in cell entry by Cryptosporidium revealed that invasion occurs rapidly; however, the parasite does not enter deep into the cytosol, but rather remains at the cell surface in a membrane bound compartment. Invasion did not stimulate rearrangement of the host cell cytoskeleton and was inhibited by cytochalasin D, even in host cells that were resistant to the drug. Our studies demonstrate that C. parvum relies on a conserved actin-myosin motor for motility and active penetration of its host cell, thus establishing this is a widely conserved feature of the Apicomplexa.