Leishmaniases are a set of tropical and sub-tropical diseases caused by protozoan parasites of the genus Leishmania whose severity ranges from self-healing cutaneous lesions to fatal visceral
infections. Leishmania parasites synthesise a wide array of cell surface and secreted
glycoconjugates that play important roles in
infection. These
glycoconjugates are particularly abundant in the promastigote form and known to be essential for establishment of
infection in the insect midgut and effective transmission to the mammalian host. Since they are rich in
galactose, their biosynthesis requires an ample supply of
UDP-galactose. This
nucleotide-
sugar arises from epimerisation of
UDP-glucose but also from an uncharacterised
galactose salvage pathway. In this study, we evaluated the role of the newly characterised
UDP-
sugar pyrophosphorylase (USP) of Leishmania major in
UDP-galactose biosynthesis. Upon deletion of the USP encoding gene, L. major lost the ability to synthesise
UDP-galactose from
galactose-1-phosphate but its ability to convert
glucose-1-phosphate into
UDP-glucose was fully maintained. Thus USP plays a role in
UDP-galactose activation but does not significantly contribute to the de novo synthesis of
UDP-glucose. Accordingly, USP was shown to be dispensable for growth and
glycoconjugate biosynthesis under standard growth conditions. However, in a mutant seriously impaired in the de novo synthesis of
UDP-galactose (due to deficiency of the
UDP-glucose pyrophosphorylase) addition of extracellular
galactose increased biosynthesis of the cell surface
lipophosphoglycan. Thus under restrictive conditions, such as those encountered by Leishmania in its natural habitat,
galactose salvage by USP may play a substantial role in biosynthesis of the
UDP-galactose pool. We hypothesise that USP recycles
galactose from the blood meal within the midgut of the insect for synthesis of the promastigote glycocalyx and thereby contributes to successful vector
infection.