INHIBITION OF PHAGOLYSOSOMAL BIOGENESIS BY THE LEISHMANIA LIPOPHOSPHOGLYCAN

Whereas amastigotes of the protozoan parasite Leishmania proliferate i nside acidic phagolysosomal vacuoles of the macrophage, vacuoles induc ed by Leishmania donovani promastigotes during initiation of infection are poorly characterized. Here, evidence is presented that interactio n of these parasitophorous vacuoles with endocytic organelles is very limited. In contrast, vacuoles formed around L. donovani mutants lacki ng the cell surface lipophosphoglycan (LPG) fuse extensively with endo somes and lysosomes. The role of LPG repeating units in the inhibition of phagosome-endosome fusion was demonstrated using two different app roaches. First, genetic complementation of the LPG-defective C3PO muta nt restored its ability to inhibit phagosome-endosome fusion to a degr ee similar to that of wild-type promastigotes. Second, opsonization of C3PO mutant cells with purified L. donovani LPG also conferred to thi s mutant the ability to inhibit phagosome-endosome fusion. Inasmuch as LPG is essential for infecting macrophages, these results suggest tha t inhibition of phagolysosomal biogenesis by LPG repeating units repre sents an intramacrophage survival strategy used by promastigotes to es tablish infection.