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Background  Infection with  Leishmania  results in a broad spectrum of pathologies where  L. infantum  and  L. donovani  cause fatal visceral leishmaniasis and  L. major  causes destructive cutaneous lesions. The identification and characterization of  Leishmania  virulence genes may define the genetic basis for these different pathologies.    Methods and Findings  Comparison of the recently completed  L. major  and  L. infantum  genomes revealed a relatively small number of genes that are absent or present as pseudogenes in  L. major  and potentially encode proteins in  L. infantum . To investigate the potential role of genetic differences between species in visceral infection, seven genes initially classified as absent in  L. major  but present in  L. infantum  were cloned from the closely related  L. donovani  genome and introduced into  L. major . The transgenic  L. major  expressing the  L. donovani  genes were then introduced into BALB/c mice to select for parasites with increased virulence in the spleen to determine whether any of the  L. donovani  genes increased visceral infection levels. During the course of these experiments, one of the selected genes (LinJ32_V3.1040 (Li1040)) was reclassified as also present in the  L. major  genome. Interestingly, only the Li1040 gene significantly increased visceral infection in the  L. major  transfectants. The Li1040 gene encodes a protein containing a putative component of an endosomal protein sorting complex involved with protein transport.    Conclusions  These observations demonstrate that the levels of expression and sequence variations in genes ubiquitously shared between  Leishmania  species have the potential to significantly influence virulence and tissue tropism.

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