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An attenuated clone of Leishmania major was produced by chemical mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and was biochemically characterized to determine the reason(s) for its loss of virulence. We found that the degree of virulence of L. major did not correlate with either the level of expression of promastigote surface protease (PSP) or with the enzymatic activity of the molecule. In contrast, the levels of lipophosphoglycan (LPG) expressed by the attenuated clone were found to be at least 6-fold less than those of virulent L. major. When the attenuated L. major was injected into BALB/c mice and allowed to revert to virulence, the degree of reversion to virulence that the parasites underwent correlated directly with the amount and form (metacyclic) of LPG expressed by the parasites. Thus, these results further implicate LPG as an important Leishmania virulence factor.

Original publication

DOI

10.1016/0166-6851(93)90067-8

Type

Journal

Molecular and biochemical parasitology

Publication Date

10/1993

Volume

61

Pages

207 - 216

Addresses

Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.

Keywords

Cell Membrane, Animals, Leishmania major, Methylnitronitrosoguanidine, Endopeptidases, Glycosphingolipids, Membrane Lipids, Caseins, Electrophoresis, Polyacrylamide Gel, Virulence, Mutagenesis, Kinetics, Molecular Weight, Time Factors