A Genomic-Based Approach Combining In Vivo Selection in Mice to Identify a Novel Virulence Gene in Leishmania

Parasites of the genus Leishmania cause a variety of human diseases that range from destructive skin lesions caused by L. major to visceral infections of the liver and spleen caused by L. donovani that result in death. The Leishmania genes responsible for these different pathologies are not known. In the present study, we used a comparative genome-based approach to introduce and over-express L. donovani genes in L. major to determine whether this results in increased virulence of L. major in visceral organs of infected mice. Through this approach, a novel gene termed Li1040 was identified that is potentially involved in protein transport and was shown to increase pathogenesis in the visceral organs in mice. The Li1040 gene may therefore represent a Leishmania virulence gene that has the potential to regulate the pathology of infection in the mammalian host. These observations help to define how Leishmania causes fatal infections in humans and therefore provide a parasite-specific target for therapy