| Abstrakt: |
The human pathogen Leishmaniasynthesizes phosphoglycans (PGs) formed by variably modified phosphodisaccharide [6-Galβ1–4Manα1-PO4] repeats and mannooligosaccharide phosphate [(Manα1–2)0–5Manα1-PO4] caps that occur lipid-bound on lipophosphoglycan, protein-bound on proteophosphoglycans, and as an unlinked form. PG repeat synthesis has been described as essential for survival and development ofLeishmaniathroughout their life cycle, including for virulence to the mammalian host. In this study, this proposal was investigated in Leishmania mexicanausing a spontaneous mutant that was fortuitously isolated from an infected mouse, and by generating a lmexlpg2gene deletion mutant (Δlmexlpg2), that lacks a Golgi GDP-Man transporter. The spontaneous mutant lacks PG repeats but synthesizes normal levels of mannooligosaccharide phosphate caps, whereas theΔlmexlpg2mutant is deficient in PG repeat synthesis and down-regulates cap expression. In contrast to expectations, both L. mexicanamutants not only retain their ability to bind to macrophages, but are also indistinguishable from wild type parasites with respect to colonization of and multiplication within host cells. Moreover, in mouse infection studies, the spontaneous L. mexicanarepeat-deficient mutant and theΔlmexlpg2mutant showed no significant difference to a wild type strain with respect to the severity of disease caused by these parasites. Therefore, at least inLeishmania mexicana, PG repeat synthesis is not an absolute requirement for virulence. |
