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dc.contributor.authorBushkin, Gary Guyen_US
dc.date.accessioned2015-08-04T18:18:58Z
dc.date.available2015-08-04T18:18:58Z
dc.date.issued2012
dc.date.submitted2012
dc.identifier.other(ALMA)contemp
dc.identifier.urihttps://hdl.handle.net/2144/12303
dc.descriptionThesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.en_US
dc.description.abstractMembers of the phylum Apicomplexa, which include many important, diverse parasites with global distribution, can be divided to two groups: those that spread by arthropod bites such as Plasmodium, the cause of malaria, and those that spread by ingestion of walled forms, such as Toxoplasma and Eimeria, cause of disseminated infections in humans and bloody diarrhea in chickens, respectively. While there is positive selection for sites of asparagine-linked glycosylation (N-glycans) in most eukaryotes that use N-glycans for quality control of glycoprotein folding , we show here that there is negative selection against N-glycans in apicomplexans that have a chloroplast-derived organelle called the apicoplast. Plasmodium has deletions of enzymes that synthesize N-glycans and therefore makes N-glycans with fewer sugar residues than other eukaryotes. In contrast, Toxoplasma has relatively long N-glycans but there is a sharply reduced density of N-glycan sites in the apicoplast-targeted proteins. Toxoplasma is spread by oocysts, which are walled parasites shed by cats, or by tissue cysts, which are walled parasites present in undercooked meat. We show here that oocyst walls of Toxoplasma and Eimeria have an inner layer in which fibrils of β-1,3-linked glucan, a major component of fungal walls, form a trabecular scaffold. Echinocandins, which are anti-fungal drugs that target glucan synthase, inhibit oocyst production by chickens infected with Eimeria, showing that the parasite glucan synthase is druggable and that β-glucan is essential for oocyst wall formation. The glucan hydrolase of Toxoplasma has a novel β-glucan-binding domain and is present in the inner layer of the oocyst wall. The oocyst walls of Toxoplasma and Eimeria, as well as the tissue cyst wall of Toxoplasma, are acid-fast like the mycobacteria wall. Toxoplasma and Eimeria have enzymes like those of mycobacteria that synthesize acid-fast lipids, which are present in organic extracts of the oocyst walls. These results suggest a new model of the oocyst wall, in which the outer layer is like that of mycobacteria, while the inner layer is like that of fungi.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.titleThe glycobiology of Plasmodium, Toxoplasma, and Eimeriaen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineCell and Molecular Biologyen_US
etd.degree.grantorBoston Universityen_US


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