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Background  One of the major challenges to leishmaniasis treatment is the emergence of parasites resistant to antimony. To study differentially expressed genes associated with drug resistance, we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (Sb III )-resistant  Leishmania infantum  lines using high-throughput RNA sequencing.    Methods  All the cDNA libraries were constructed from promastigote forms of each line, sequenced and analyzed using STAR for mapping the reads against the reference genome ( L. infantum  JPCM5) and DESeq2 for differential expression statistical analyses. All the genes were functionally annotated using sequence similarity search.    Results  The analytical pipeline considering an adjusted  p -value < 0.05 and fold change > 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and Sb III -resistant  L. infantum  lines. Out of 933 DE transcripts, 504 presented functional annotation and 429 were assigned as hypothetical proteins. A total of 837 transcripts were upregulated and 96 were downregulated in the Sb III -resistant  L. infantum  line. Using this DE dataset, the proteins were further grouped in functional classes according to the gene ontology database. The functional enrichment analysis for biological processes showed that the upregulated transcripts in the Sb III -resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host–parasite interaction, cellular process and other categories. The downregulated transcripts in the Sb III -resistant line are assigned in the GO categories: ribonucleoprotein complex, ribosome biogenesis, rRNA processing, nucleosome assembly and translation.    Conclusions  The transcriptomic profile of  L. infantum  showed a robust set of genes from different metabolic pathways associated with the antimony resistance phenotype in this parasite. Our results address the complex and multifactorial antimony resistance mechanisms in  Leishmania , identifying several candidate genes that may be further evaluated as molecular targets for chemotherapy of leishmaniasis.

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines