REVERSION TO VIRULENCE IN LEISHMANIA-MAJOR CORRELATES WITH EXPRESSIONOF SURFACE LIPOPHOSPHOGLYCAN

An attenuated clone of Leishmania major was produced by chemical mutag enesis with N-methyl-N'-nitro-N-nitrosoguanidineand 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 leve ls of lipophosphoglycan (LPG) expressed by the attenuated clone were f ound 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 r evert to virulence, the degree of reversion to virulence that the para sites underwent correlated directly with the amount and form (metacycl ic) of LPG expressed by the parasites. Thus, these results further imp licate LPG as an important Leishmania virulence factor.