Screening Leishmania donovani‐specific genes required for visceral infection
- 5 July 2010
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 77 (2), 505-517
- https://doi.org/10.1111/j.1365-2958.2010.07230.x
Abstract
Comparison of the Leishmania infantum genome with Leishmania braziliensis and Leishmania major genomes has identified 25 L. infantum species-specific genes that are absent or pseudogenes in L. major and L. braziliensis. To determine whether these L. infantum species-specific genes are involved in visceral Leishmania infection, we cloned the orthologues of 14 L. infantum species-specific genes from the genetically closely related Leishmania donovani and introduced them into L. major. Two of these L. donovani species-specific genes were found to significantly increase L. major survival in visceral organs in BALB/c mice. One (orthologue of LinJ28_V3.0340; Ld2834) of these two genes was further investigated. The L. donovani Ld2834 null mutants displayed dramatically reduced virulence in BALB/c mice and were unable to survive in axenic amastigote culture conditions arguing that Ld2834 plays a crucial role in enabling L. donovani survive at the increased temperature typically associated with visceral organs. Ld2834 encodes a 50 kDa protein that is localized in the cytoplasma and has no significant sequence similarity with other known genes. This study validates the importance of comparative genomics for understanding Leishmania species pathology and argues that Leishmania species-specific genes play important roles in tissue tropism and virulence.Keywords
This publication has 35 references indexed in Scilit:
- Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic BackgroundsPLoS Neglected Tropical Diseases, 2009
- Demonstration of Genetic Exchange During Cyclical Development of Leishmania in the Sand Fly VectorScience, 2009
- A Genomic-Based Approach Combining In Vivo Selection in Mice to Identify a Novel Virulence Gene in LeishmaniaPLoS Neglected Tropical Diseases, 2008
- Comparative genomics: From genotype to disease phenotype in the leishmaniasesInternational Journal for Parasitology, 2007
- Comparative genomic analysis of three Leishmania species that cause diverse human diseaseNature Genetics, 2007
- Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomyProceedings of the National Academy of Sciences of the United States of America, 2007
- Increased transmission potential of Leishmania major/Leishmania infantum hybridsInternational Journal for Parasitology, 2007
- Uncommon clinical presentations of cutaneous leishmaniasis in SudanTransactions of the Royal Society of Tropical Medicine and Hygiene, 2005
- Advances in leishmaniasisThe Lancet, 2005
- The Genome of the Kinetoplastid Parasite, Leishmania majorScience, 2005