Abstract
BackgroundThe leishmaniasis are parasitic diseases caused by protozoans of the genus Leishmania, highly divergent eukaryotes, characterized by unique biological features. To survive in both the mammalian hosts and insect vectors, these pathogens make use of a number of mechanisms, many of which are associated with parasite specific proteases. The metalloprotease GP63, the major Leishmania surface antigen, has been found to have multiple functions required for the parasite’s survival. GP63 is encoded by multiple genes and their copy numbers vary considerably between different species and are increased in those from the subgenus Viannia, including L. braziliensis.ResultsBy comparing multiple sequences from Leishmania and related organisms this study sought to characterize paralogs in silico, evaluating their differences and similarities and the implications for the GP63 function. The Leishmania GP63 genes are encoded on chromosomes 10, 28 and 31, with the genes from the latter two chromosomes more related to genes found in insect or plant parasites. Those from chromosome 10 have experienced independent expansions in numbers in Leishmania, especially in L. braziliensis. These could be clustered in three groups associated with different mRNA 3′ untranslated regions as well as distinct C-terminal ends for the encoded proteins, with presumably distinct expression patterns and subcellular localizations. Sequence variations between the chromosome 10 genes were linked to intragenic recombination events, mapped to the external surface of the proteins and predicted to be immunogenic, implying a role against the host immune response.ConclusionsOur results suggest a greater role for the sequence variation found among the chromosome 10 GP63 genes, possibly related to the pathogenesis of L. braziliensis and closely related species within the mammalian host. They also indicate different functions associated to genes mapped to different chromosomes. For the chromosome 10 genes, variable subcellular localizations were found to be most likely associated with multiple functions and target substrates for this versatile protease.
Highlights
The leishmaniasis are parasitic diseases caused by protozoans of the genus Leishmania, highly divergent eukaryotes, characterized by unique biological features
Search for new L. braziliensis Glycoprotein 63 (GP63) paralogs The early studies based on hybridization assays [23, 24] had suggested that the total number of GP63 genes found within Leishmania species belonging to the Viannia subgenus is greater than the number of genes available at the TriTrypDB database and identified after the L. braziliensis genome sequencing and annotation
To do this we performed a search in the L. braziliensis genome using the Hidden Markov Models (HMMs) methodology [31], carried out after a grouping of the entire proteome set from different Leishmania species
Summary
The leishmaniasis are parasitic diseases caused by protozoans of the genus Leishmania, highly divergent eukaryotes, characterized by unique biological features To survive in both the mammalian hosts and insect vectors, these pathogens make use of a number of mechanisms, many of which are associated with parasite specific proteases. The leishmaniasis are parasitic infectious diseases caused by flagellated protozoa belonging to the genus Leishmania, family Trypanosomatidae, and which are transmitted by sandflies of the genera Phlebotomus or Lutzomyia. It was later found to be bound to the cell membrane through a GlycosylPhosphatidylInositol (GPI) anchor and was identified as an important virulence factor This is a zinc-dependent metalloproteinase, which belongs to the peptidase family M8 and the metzincin class and includes conserved features such as the motif HEXXHXXGXXH and a pro-peptide located in the protein’s N-terminal region that renders the proenzyme inactive during translation and is removed during its maturation and activation. The GP63 proteins include an N-terminal signal sequence which directs them to the endoplasmic reticulum and to the Leishmania secretory pathway [7, 8]
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