Leishmaniasis is considered a neglected tropical disease for which there is no vaccine. On the other hand, first-line drugs have shown an increase in therapeutic failures, among other causes due to the acquisition of resistance by their etiological agent, depending on the characteristics of each species (eg, clinical manifestation and geographic distribution). Thus, understanding the mechanism used by the parasite to survive under the pressure of treatments by identifying probable common and specific therapeutic targets is important for the control of leishmaniasis. However, to date no analysis has been performed comparing gene expression between Leishmania species that exhibit different genetic and biological characteristics reflected in the associated differential clinical manifestations. Here, we apply comparative analyzes of the transcriptomic profiles of lines with experimentally induced resistance to trivalent antimony (SbIII) of five species of medical importance (Subgenus L. (Leishmania): L. donovani, L. infantum and L. amazonensis; Subgenus L. (Viannia): L. panamensis and L. braziliensis), causing different clinical manifestations (which are generally cutaneous Leishmaniasis for L. panamensis and L. amazonensis, mucocutaneous for L. braziliensis and visceral for L. donovani and L. infantum) a starting from functional analysis of ontology and assignment of orthologous groups. The resistant lines had differential responses mainly in metabolic processes, compound binding and membrane components with respect to their sensitive counterpart. metabolic, binding to membrane compounds and components relative to their sensitive counterpart. Differentially expressed orthologous genes assigned to species-specific responses predominated with a total of 1426 self genes. At the level of the response by subgenus, no shared genes were found among the species belonging to L. (Leishmania) and only 7 were found among those belonging to L. (Viannia). No differentially expressed gene was found in common among the 5 species, but two common upregulated orthologous genes were found among 4 species (L. donovani, L. braziliensis, L. amazonensis and L. panamensis) referred to an RNA-binding protein and the NAD (P) H cytochrome B5 oxidoreductase complex, associated with transcriptional control and de novo synthesis of linoleic acid, important in the mechanisms of resistance to antimonials. These patterns probably obey the multifactorial phenomenon of drug resistance, dependent on the intrinsic characteristics of the parasite and the environment. Therefore, species-specific approaches are more advisable for proposing potential therapeutic targets.
publication date
February 16, 2021 11:44 PM
Research
keywords
Comparative genomics and transcriptomics of Leishmania
Effectiveness of trivalent antimony (SbIII) against leishmania
