Journal article
Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts
S Lopaticki, ASP Yang, A John, NE Scott, JP Lingford, MT O'Neill, SM Erickson, NC McKenzie, C Jennison, LW Whitehead, DN Douglas, NM Kneteman, ED Goddard-Borger, JA Boddey
Nature Communications | NATURE PUBLISHING GROUP | Published : 2017
Abstract
O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms..
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Awarded by National Science Foundation
Funding Acknowledgements
We thank the Melbourne Red Cross for erythrocytes, the US Naval Medical Research Centre for HC-04 cells, Fidel Zavala for PfCSP antibodies, Alan Cowman for PfTRAP and PfAldolase antibodies and Andrew Webb, Liana Mackiewicz, Alexandra Garnham, and Melissa Hobbs for valuable technical assistance. This work was supported by the Australian National Health and Medical Research Council (Project Grants 1049811 and 1100164), Human Frontiers Science Program (RGY0073/2012), Ramaciotti Foundation Establishment Grants (3197/2010 and ES2013/0111) and the University of Melbourne Early Career Researcher Grant Scheme (603107). We also acknowledge Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. A.S.P.Y., A.J., and N.C.M. were supported by Australian Postgraduate Awards, N.E.S. was supported by a NHMRC Overseas Biomedical Fellowship (1037373), E.D.G.-B. was supported by a VESKI Innovation Fellowship and J.A.B. was supported by an Australian Research Council QEII Fellowship (DP110105395).