Leishmania are intracellular protozoan parasites that reside primarily in host mononuclear phagocytes. Infection of host macrophages is initiated by infective promastigote stages and perpetuated by an obligate intracellular amastigote stage. Studies undertaken over the last decade have shown that the composition of the complex surface glycocalyx of these stages (comprising lipophosphoglycan, GPI-anchored glycoproteins, proteophosphoglycans and free GPI glycolipids) changes dramatically as promastigotes differentiate into amastigotes. Marked stage-specific changes also occur in the expression of other plasma membrane components, including type-1, polytopic and peripheral membrane proteins, reflecting the distinct microbicidal responses and nutritional environments encountered by these stages. More recently, a number of Leishmania mutants lacking single or multiple surface components have been generated. While some of these mutants are less virulent than wild type parasites, many of these mutants exhibit only mild or no loss of virulence. These studies suggest that, 1) the major surface glycocalyx components of the promastigote stage (i.e. LPG, GPI-anchored proteins) only have a transient or minor role in macrophage invasion, 2) that there is considerable functional redundancy in the surface glycocalyx and/or loss of some components can be compensated for by the acquisition of equivalent host glycolipids, 3) the expression of specific nutrient transporters is essential for life in the macrophage and 4) the role(s) of some surface components differ markedly in different Leishmania species. These mutants will be useful for identifying other surface or intracellular components that are required for virulence in macrophages.
[1]
A. Debrabant,et al.
Members of a unique histidine acid phosphatase family are conserved amongst a group of primitive eukaryotic human pathogens
,
2003,
Molecular and Cellular Biochemistry.
[2]
A. Prasad,et al.
Ca2+ signaling in the transformation of promastigotes to axenic amastigotes of Leishmania donovani
,
2001,
Molecular and Cellular Biochemistry.
[3]
S. Castanys,et al.
Leishmania donovani Resistance to Miltefosine Involves a Defective Inward Translocation of the Drug
,
2003,
Antimicrobial Agents and Chemotherapy.
[4]
R. Teasdale,et al.
Secretory Pathway of Trypanosomatid Parasites
,
2002,
Microbiology and Molecular Biology Reviews.
[5]
T. Ilg,et al.
Glycosylation Defects and Virulence Phenotypes ofLeishmania mexicana Phosphomannomutase and Dolicholphosphate-Mannose Synthase Gene Deletion Mutants
,
2001,
Molecular and Cellular Biology.
[6]
M. Kavanaugh,et al.
Functional expression of a myo-inositol/H+ symporter from Leishmania donovani
,
1995,
Molecular and cellular biology.
[7]
J. Jauniaux,et al.
A gene from the variant surface glycoprotein expression site encodes one of several transmembrane adenylate cyclases located on the flagellum of Trypanosoma brucei
,
1992,
Molecular and cellular biology.