During growth within the sand fly and within axenic culture, Leishmania promastigotes undergo differentiation from a non-infective to an infective or metacyclic stage which is uniquely adapted for life in the vertebrate. For some species of Leishmania (L. donovani and L. major) this development is accompanied by a substantial modification of the surface lipophosphoglycan (LPG) which is the major surface glycoconjugate of these cells. During metacyclogenesis, the LPG is developmentally modified such that it no longer binds the lectin PNA, it expresses a novel carbohydrate epitope, and the number of phosphorylated saccharide units expressed increases 2-3 fold. Immunogold labeling of the surface LPG revealed a 10nm thickening in the LPG coat, which assumed a filamentous appearance on freeze-fracture preparations. The LPG on Old Word promastigotes forms a densely packed surface coat which effectively masks other surface molecules, such as GP63. We have presented evidence that the elongation of the LPG serves to promote the complement resistance of inoculated metacyclics by preventing insertion of the membrane attack complex into the membrane. LPG does not appear to be expressed on the surface of L. major L. donovani amastigotes, suggesting that the surface coat is a stage specific structure which undoubtedly influences the survival and behavior of the parasite within the alimentary tract of the sand fly. These vector biological studies have only recently been initiated. LPG has also been investigated on New World species, and while metacyclic promastigotes of these species express saccharide units which are altered in composition, there is no elongation of the LPG, and this is consistent with the continued serum susceptibility of these infective forms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000256-09
Application #
3809590
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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