A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania

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 di...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2008-06, Vol.2 (6), p.e248-e248
Main Authors: Zhang, Wen-Wei, Peacock, Christopher S, Matlashewski, Greg
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Blotting, Northern
Blotting, Southwestern
Blotting, Western
Female
Genes
Genetics and Genomics/Comparative Genomics
Genetics and Genomics/Functional Genomics
Genome, Protozoan - genetics
Infectious Diseases/Neglected Tropical Diseases
Infectious Diseases/Tropical and Travel-Associated Diseases
Leishmania
Leishmania - genetics
Leishmania - metabolism
Leishmania - pathogenicity
Leishmania infantum - genetics
Leishmania infantum - metabolism
Leishmania infantum - pathogenicity
Leishmania major - genetics
Leishmania major - metabolism
Leishmania major - pathogenicity
Medical research
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Molecular Sequence Data
Parasites
Parasitic diseases
Polymerase Chain Reaction
Proteins
Protozoan Proteins - chemistry
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Sequence Homology, Amino Acid
Tropical diseases
Virulence - genetics
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Summary: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. 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. 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.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0000248