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Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of Trivalent Sodium Stibogluconate

ABSTRACT: Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of Trivalent Sodium Stibogluconate

PROVIDER: PRJEB33484 | ENA |

REPOSITORIES: ENA

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Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes

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

Project description:BackgroundIn 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.MethodsHere, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes.ResultsA 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 (SbIII) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites.ConclusionsThis work identified global transcriptomic changes in an in vitro-adapted strain in response to SbIII. 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.

| S-EPMC6626383 | biostudies-literature

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Project description:To determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes A genome-wide transcriptional analysis was performed by comparing the gene expression profiles of control DLs and live amastigote-hosting DLs from both mouse strains. Dendritic Leucocytes were generated in vitro from bone marrow progenitors (C57Bl/6 and DBA/2 mice). Leishmania amazonensis amastigotes were purified from mouse cutaneous lesions and were added to DL cultures. After 24h, and following a sorting procedure, only BMDls housing living amastigotes were selected for total RNA extraction. Three Biological replicates per condition were run.

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