Mannosyltransferase (GPI-14) overexpression protects promastigote and amastigote forms of Leishmania braziliensis against trivalent antimony

Ribeiro, Christiana Vargas; Rocha, Bruna Fonte Boa; Moreira, Douglas de Souza; Peruhype-Magalhães, Vanessa; Murta, Silvane Maria Fonseca

doi:10.1186/s13071-019-3305-2

“…See Additional file 1: Table S1 for complete data Some of the differentially expressed transcripts identified in this study corroborate previous proteomic analysis of antimony-resistant and -susceptible L. infantum lines [22]. In addition, some upregulated transcripts identified in this study were also previously investigated by our group, such as gamma-glutamylcysteine synthetase [41] elongation factor 2 [42] and mannosyltransferase [43], and these previous results confirmed that they are associated with antimony resistance phenotype in Leishmania spp.…”

Section: Discussionsupporting

confidence: 89%

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Andrade¹,

Gonçalves

²

,

Liarte

³

et al. 2020

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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 (SbIII)-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 SbIII-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 SbIII-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 SbIII-resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host–parasite interaction, cellular process and other categories. The downregulated transcripts in the SbIII-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.

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“…Some of the differentially expressed transcripts identi ed in this study corroborate previous proteomic analysis of antimony resistant and susceptible L. infantum lines [22]. In addition, some upregulated transcripts identi ed in this study were also previously investigated by our group, such as gamma-glutamylcysteine synthetase [41] elongation factor 2 [42] and mannosyltransferase [43] and these previous results con rmed that they are associated with antimony-resistance phenotype in Leishmania spp.…”

Section: Discussionsupporting

confidence: 89%

“…Our data showed that one transcript encoding this enzyme is 2.54-fold upregulated in the LiSbR line (Additional le 2: Table S2). Interestingly, our group overexpressed the GPI-14 gene in L. braziliensis and observed the involvement of the GPI-14 enzyme in the Sb III -resistance phenotype of L. braziliensis [43].…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Andrade

¹

,

Gonçalves

²

,

Liarte

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

Background: One of the major challenges for leishmaniasis treatment is the emergence of parasites resistant to antimony. In order to study differentially expressed genes associated with drug resistance we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (SbIII)-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 lower than 0.05 and fold change greater than 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and SbIII-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 SbIII-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 SbIII-resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host-parasite interaction, cellular process and other categories. The downregulated transcripts in the SbIII-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 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.

show abstract

“…Some of the differentially expressed transcripts identi ed in this study corroborate previous proteomic analysis of antimony resistant and susceptible L. infantum lines [22]. In addition, some upregulated transcripts identi ed in this study were also previously investigated by our group, such as gammaglutamylcysteine synthetase [41] elongation factor 2 [42] and mannosyltransferase [43] and these previous results con rmed that they are associated with antimony-resistance phenotype in Leishmania spp.…”

Section: Discussionsupporting

confidence: 89%

“…Our data showed that one transcript encoding this enzyme is 2.54-fold upregulated in the LiSbR line (Additional le 2). Interestingly, our group overexpressed the GPI-14 gene in L. braziliensis and observed the involvement of the GPI-14 enzyme in the Sb III -resistance phenotype of L. braziliensis [43].…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Andrade

¹

,

Gonçalves

²

,

Liarte

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

Background: One of the major challenges for leishmaniasis treatment is the emergence of parasites resistant to antimony. In order to study differentially expressed genes associated with drug resistance we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (SbIII)-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 lower than 0.05 and fold change greater than 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and SbIII-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 SbIII-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 SbIII-resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host-parasite interaction, cellular process and other categories. The downregulated transcripts in the SbIII-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 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.

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Mannosyltransferase (GPI-14) overexpression protects promastigote and amastigote forms of Leishmania braziliensis against trivalent antimony

Cited by 7 publications

References 33 publications

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines

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