Location: Animal Parasitic Diseases LaboratoryTitle: Beta-1,3-glucan1,3-glucan, a druggable target, forms a trabecular scaffold in the oocyst walls of Toxoplasma and Eimeria
|BUSKHIN, GUY - Boston University|
|BULLITT, ESTHER - Boston University Medical School|
|COSTELLO, CATHERINE - Boston University Medical School|
|ROBBINS, PHILLIP - Boston University|
|SAMUELSON, JOHN - Boston University|
Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/8/2012
Publication Date: 9/30/2012
Citation: Buskhin, G., Dubey, J.P., Miska, K.B., Bullitt, E., Costello, C.E., Robbins, P.W., Samuelson, J. 2012. Beta-1,3-glucan1,3-glucan, a druggable target, forms a trabecular scaffold in the oocyst walls of Toxoplasma and Eimeria. mBio. 3(5):e00258-12.
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 under-cooked meat from infected animals as well as other food or water if contaminated with oocysts. There are no effective drugs to kill the oocysts. In the present study, authors found that the part of the Toxoplasma oocyst wall contains a glucan, which is a major component of fungal and plant walls, suggesting that antifungal medicines and herbicides might kill Toxoplasma oocysts. The results will be of interest to biologists, parasitologists, and public health workers.
Technical Abstract: Toxoplasma gondii is a human pathogen that spreads by ingestion of oocysts in cat feces or tissue cysts in raw meat. Eimeria species are major pathogens of livestock that also spread by infectious oocysts. Beta-1,3-glucan, a major component of fungal and plant walls, is the target of anti-fungal drugs called echinocandins. Here we show that oocyst walls label with four reagents that bind ß-1,3-glucan: macrophage Dectin-1, antibodies to ß-1,3-glucan, the glucan-binding domain (GBD) of a Schizosaccharomyces glucan hydrolase, and a novel GBD of a Toxoplasma glucan hydrolase. A trabecular scaffold in the inner layer of the oocyst wall contains fibrils of ß-1,3-glucan. Treatment of Eimeria-infected chickens with echinocandins caused a marked decrease in oocyst recovery, demonstrating the importance of ß-1,3-glucan to oocyst wall formation. Beta-1,3-glucan is absent from the wall of Toxoplasma tissue cysts, and knock-out of the Toxoplasma glucan synthase gene does not affect tissue cyst formation in vitro. In summary, ß-1,3-glucan is an important component of oocyst walls but is not a component of sporocyst and tissue cyst walls.