Expression of a Leishmaniadonovani nucleotide sugar transporter in Leishmaniamajor enhances survival in visceral organs.

Leishmania donovani and Leishmaniainfantum infections cause fatal visceral leishmaniasis, and Leishmaniamajor causes self healing cutaneous lesions. It is poorly understood what genetic differences between these Leishmania species are responsible for the different pathologies of infection. To investigate whether L.donovani species-specific genes are involved in visceral Leishmania infection, we have examined a L.donovani species-specific gene Ld1590 (ortholog of LinJ15_V3.0900) that is a pseudogene in L.major. We have previously shown that transgenic expression of L.donovani Ld1590 in L.major significantly increased the liver and spleen parasite burdens in infected BALB/c mice. In this study we report that Ld1590 potentially encodes a nucleotide sugar transporter (NST) which localizes in the L.donovani Golgi apparatus. Surprisingly, although transgenic expression of the Ld1590 NST increased L.major survival in visceral organs, deletion of Ld1590 NST in L.donovani had no significant effect on L.donovani survival in mice. These observations suggest that loss of the functional Ld1590 gene in L.major may have been associated with reduced virulence in visceral organs in its animal reservoir and could have contributed to L.major's tropism for cutaneous infections.