C-Mannosylation of Toxoplasma gondii proteins promotes attachment to host cells and parasite virulence

Albuquerque-Wendt, A. , Jacot, D., Dos Santos Pacheco, N., Seegers, C., Zarnovican, P., Buettner, F. F.R., Bakker, H., Soldati-Favre, D. and Routier, F. H. (2020) C-Mannosylation of Toxoplasma gondii proteins promotes attachment to host cells and parasite virulence. Journal of Biological Chemistry, 295(4), pp. 1066-1076. (doi: 10.1074/jbc.ra119.010590) (PMID:31862733) (PMCID:PMC6983843)

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Abstract

C-Mannosylation is a common modification of thrombospondin type 1 repeats present in metazoans and recently identified also in apicomplexan parasites. This glycosylation is mediated by enzymes of the DPY19 family that transfer α-mannoses to tryptophan residues in the sequence WX2WX2C, which is part of the structurally essential tryptophan ladder. Here, deletion of the dpy19 gene in the parasite Toxoplasma gondii abolished C-mannosyltransferase activity and reduced levels of the micronemal protein MIC2. The loss of C-mannosyltransferase activity was associated with weakened parasite adhesion to host cells and with reduced parasite motility, host cell invasion, and parasite egress. Interestingly, the C-mannosyltransferase–deficient Δdpy19 parasites were strongly attenuated in virulence and induced protective immunity in mice. This parasite attenuation could not simply be explained by the decreased MIC2 level and strongly suggests that absence of C-mannosyltransferase activity leads to an insufficient level of additional proteins. In summary, our results indicate that T. gondii C-mannosyltransferase DPY19 is not essential for parasite survival, but is important for adhesion, motility, and virulence.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Albuquerque-Wendt, Ms Andreia
Creator Roles:
Albuquerque-Wendt, A.Conceptualization, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing – original draft, Writing – review and editing
Authors: Albuquerque-Wendt, A., Jacot, D., Dos Santos Pacheco, N., Seegers, C., Zarnovican, P., Buettner, F. F.R., Bakker, H., Soldati-Favre, D., and Routier, F. H.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:20 December 2019
Copyright Holders:Copyright © 2020 ASBMB
First Published:First published in Journal of Biological Chemistry 295(4): 1066-1076
Publisher Policy:Reproduced under a Creative Commons License

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