Characterisation of a Leishmania mexicana knockout lacking guanosine diphosphate-mannose pyrophosphorylase
- Author(s)
- Stewart, J; Curtis, J; Spurck, TP; Ilg, T; Garami, A; Baldwin, T; Courret, N; McFadden, GI; Davis, A; Handman, E;
- Details
- Publication Year 2005-07,Volume 35,Issue #8,Page 861-873
- Journal Title
- INTERNATIONAL JOURNAL FOR PARASITOLOGY
- Publication Type
- Journal Article
- Abstract
- In eukaryotes, the enzyme GDP-mannose pyrophosphorylase (GDP-MP) is essential for the formation of GDP-mannose, the donor of activated mannose for all glycosylation reactions. Unlike other eukaryotes, where deletion of GDP-mannose pyrophosphory lase is lethal, deletion of this gene in Leishmania mexicana has no effect on viability, but leads to the generation of avirulent parasites. In this study, we show that the null mutants have a perturbed morphology and cytokinesis, retarded growth and increased adherence to the substratum where they form large colonies. The null mutants attach avidly to mouse macrophages, but unlike the wild type organisms, they do not bind to the complement receptor 3 and are slow to induce phagocytosis. Once internalised, they localise to the phagolysosome, but in contrast to wild type organisms which transform into the intracellular amastigote and establish in the macrophage, they are cleared by 24 h in culture and by 5 h in vivo. The null mutants are hypersensitive to human but not mouse complement and to temperature and acidic pH. Surprisingly, in view of the lack of several known host-protective antigens, injection of the mutant parasites into BALB/c mice confers significant and long lasting protection against infection, suggesting that these temperature sensitive mutants are an attractive candidate for a live attenuated vaccine. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- PROTOZOAN PARASITE LEISHMANIA; CUTANEOUS LEISHMANIASIS; VIRULENCE FACTOR; PROMASTIGOTES; MICE; LIPOPHOSPHOGLYCAN; GLYCOSYLATION; AMASTIGOTES; MACROPHAGES; PERSISTENCE
- Publisher's Version
- https://doi.org/10.1016/j.ijpara.2005.03.008
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- Refer to copyright notice on published article.
Creation Date: 2005-07-01 12:00:00