Stage-specific binding of Leishmania donovani to the sand fly vector midgut is regulated by conformational changes in the abundant surface lipophosphoglycan.

Details

Ressource 1Download: 019. Sacks et al.pdf (3212.15 [Ko])
State: Public
Version: author
License: Not specified
Serval ID
serval:BIB_7DF288AFA738
Type
Article: article from journal or magazin.
Collection
Publications
Title
Stage-specific binding of Leishmania donovani to the sand fly vector midgut is regulated by conformational changes in the abundant surface lipophosphoglycan.
Journal
Journal of Experimental Medicine
Author(s)
Sacks D.L., Pimenta P.F., McConville M.J., Schneider P., Turco S.J.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Publication state
Published
Issued date
1995
Volume
181
Number
2
Pages
685-697
Language
english
Abstract
The life cycle of Leishmania parasites within the sand fly vector includes the development of extracellular promastigotes from a noninfective, procyclic stage into an infective, metacyclic stage that is uniquely adapted for transmission by the fly and survival in the vertebrate host. These adaptations were explored in the context of the structure and function of the abundant surface lipophosphoglycan (LPG) on Leishmania donovani promastigotes. During metacyclogenesis, the salient structural feature of L. donovani LPG is conserved, involving expression of a phosphoglycan chain made up of unsubstituted disaccharide-phosphate repeats. Two important developmental modifications were also observed. First, the size of the molecule is substantially increased because of a twofold increase in the number of phosphorylated disaccharide repeat units expressed. Second, there is a concomitant decrease in the presentation of terminally exposed sugars. This later property was indicated by the reduced accessibility of terminal galactose residues to galactose oxidase and the loss of binding by the lectins, peanut agglutinin, and concanavalin A, to metacyclic LPG in vivo and in vitro. The loss of lectin binding was not due to downregulation of the capping oligosaccharides as the same beta-linked galactose or alpha-linked mannose-terminating oligosaccharides were present in both procyclic and metacyclic promastigotes. The capping sugars on procyclic LPG were found to mediate procyclic attachment to the sand fly midgut, whereas these same sugars on metacyclic LPG failed to mediate metacyclic binding. And whereas intact metacyclic LPG did not inhibit procyclic attachment, depolymerized LPG inhibited as well as procyclic LPG, demonstrating that the ligands are normally buried. The masking of the terminal sugars is attributed to folding and clustering of the extended phosphoglycan chains, which form densely distributed particulate structures visible on fracture-flip preparations of the metacyclic surface. The exposure and subsequent masking of the terminal capping sugars explains the stage specificity of promastigote attachment to and release from the vector midgut, which are key events in the development of transmissible infections in the fly.
Keywords
Animals, Carbohydrate Conformation, Carbohydrate Sequence, Digestive System/parasitology, Female, Glycosphingolipids/chemistry, Glycosphingolipids/physiology, Leishmania donovani/growth &amp, development, Leishmania donovani/physiology, Molecular Sequence Data, Oligosaccharides/chemistry, Psychodidae/parasitology
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
17/01/2020 13:28
Usage data