Dataset Information

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.

ABSTRACT:

Background

In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis.

Methods

Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes.

Results

A total of 723 differentially expressed genes were identified between resistant and sensitive lines. Comparative transcriptomic analysis revealed that genes encoding proteins involved in metabolism (fatty acids) and stress response, as well as those associated with antimony resistance in other Leishmania species, were upregulated in the antimony-resistant line. Most importantly, we observed upregulation of genes encoding autophagy proteins, suggesting that in the presence of trivalent stibogluconate (Sb^III) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites.

Conclusions

This work identified global transcriptomic changes in an in vitro-adapted strain in response to Sb^III. Our results provide relevant information to continue understanding the mechanism used by parasites of the subgenus Leishmania (L. amazonensis) to generate an antimony-resistant phenotype.

SUBMITTER: Patino LH

PROVIDER: S-EPMC6626383 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.

Patino Luz H LH Muskus Carlos C Ramírez Juan David JD

Parasites & vectors 20190712 1

<h4>Background</h4>In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis.<h4>Methods</h4>Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -s ...[more]

PMID: 31300064

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Project description:BackgroundLeishmaniasis is a neglected tropical disease caused by several species of Leishmania. The resistance phenotype of these parasites depends on the characteristics of each species, which contributes to increased therapeutic failures. Understanding the mechanism used by the parasite to survive under treatment pressure in order to identify potential common and specific therapeutic targets is essential for the control of leishmaniasis. The aim of this study was to investigate the expression profiles and potential shared and specific resistance markers of the main Leishmania species of medical importance [subgenus L. (Leishmania): L. donovani, L. infantum and L. amazonensis; subgenus L. (Viannia): L. panamensis and L. braziliensis)] resistant and sensitive to trivalent stibogluconate (SbIII).MethodsWe conducted comparative analysis of the transcriptomic profiles (only coding sequences) of lines with experimentally induced resistance to SbIII from biological replicates of five Leishmania species available in the databases of four articles based on ortholog attribution. Simultaneously, we carried out functional analysis of ontology and reconstruction of metabolic pathways of the resulting differentially expressed genes (DEGs).ResultsResistant lines for each species had differential responses in metabolic processes, compound binding, and membrane components concerning their sensitive counterpart. One hundred and thirty-nine metabolic pathways were found, with the three main pathways comprising cysteine and methionine metabolism, glycolysis, and the ribosome. Differentially expressed orthologous genes assigned to species-specific responses predominated, with 899 self-genes. No differentially expressed genes were found in common among the five species. Two common upregulated orthologous genes were found among four species (L. donovani, L. braziliensis, L. amazonensis, and L. panamensis) related 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, critical mechanisms in resistance to antimonials.ConclusionHerein, we identified potential species-specific genes related to resistance to SbIII. Therefore, we suggest that future studies consider a treatment scheme that is species-specific. Despite the limitations of our study, this is the first approach toward unraveling the pan-genus genetic mechanisms of resistance in leishmaniasis.

Dataset Information

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.

Background

Methods

Results

Conclusions

Publications

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.

Similar Datasets

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