Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/58650
Type
ArticleCopyright
Restricted access
Embargo date
2099-12-31
Collections
Metadata
Show full item record
COMPARATIVE TRANSCRIPTOMIC ANALYSIS OF ANTIMONY RESISTANT AND SUSCEPTIBLE LEISHMANIA INFANTUM LINES
Leishmania infantum chagasi
Antimony resistance
Proteome
2-DE
Cyclophilin-A
Pteridine reductase
ryparedoxin peroxidase
Author
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Estadual de Montes Claros. Laboratório de Epidemiologia e Biocontrole de Microrganismos. Montes Claros, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal do Piauí. Terezina, PI, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade Estadual de Santa Cruz. Laboratório de Proteômica. Ilheús, BA, Brazil
Universidade Estadual de Santa Cruz. Laboratório de Proteômica. Ilheús, BA, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal do Piauí. Terezina, PI, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade Estadual de Santa Cruz. Laboratório de Proteômica. Ilheús, BA, Brazil
Universidade Estadual de Santa Cruz. Laboratório de Proteômica. Ilheús, BA, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Abstract
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.
Keywords
Leishmania braziliensisLeishmania infantum chagasi
Antimony resistance
Proteome
2-DE
Cyclophilin-A
Pteridine reductase
ryparedoxin peroxidase
Share