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Silvane Maria Fonseca Murta
Centro de Pesquisas René Rachou FIOCRUZ
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8523-2155
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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.
Keywords
Leishmania infantum, trivalent antimony, resistance, RNA sequencing, transcriptome, differentially expressed genes
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CURRENT STATUS: Published
View the published article at Parasites & Vectors.
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Posted 17 Nov, 2020
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Editorial decision: Accept
On 11 Nov, 2020
Editor assigned
On 11 Nov, 2020
Submission checks complete
On 11 Nov, 2020
Editor invited
On 11 Nov, 2020
No comments provided
Editorial decision: Minor Revision
On 04 Nov, 2020
Review #1 received
Received 03 Nov, 2020
Reviewer #1 agreed
On 02 Nov, 2020
Reviewers invited
Invitations sent on 01 Nov, 2020
Editor invited
On 31 Oct, 2020
Editor assigned
On 31 Oct, 2020
Submission checks complete
On 31 Oct, 2020
No comments provided
Review #2 received
Received 02 Oct, 2020
Editorial decision: Major Revision
On 02 Oct, 2020
Review #1 received
Received 17 Aug, 2020
Reviewer #2 agreed
On 11 Aug, 2020
Reviewer #1 agreed
On 10 Aug, 2020
Reviewers invited
Invitations sent on 09 Aug, 2020
Editor assigned
On 08 Aug, 2020
First submitted
On 07 Aug, 2020
Submission checks complete
On 07 Aug, 2020
Editor invited
On 07 Aug, 2020
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Subject Areas
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See the published version of this preprint at Parasites & Vectors.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Silvane Maria Fonseca Murta
Centro de Pesquisas René Rachou FIOCRUZ
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8523-2155
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Parasites & Vectors.
Version 3
Posted 17 Nov, 2020
No community comments so far
Editorial decision: Accept
On 11 Nov, 2020
Editor assigned
On 11 Nov, 2020
Submission checks complete
On 11 Nov, 2020
Editor invited
On 11 Nov, 2020
No comments provided
Editorial decision: Minor Revision
On 04 Nov, 2020
Review #1 received
Received 03 Nov, 2020
Reviewer #1 agreed
On 02 Nov, 2020
Reviewers invited
Invitations sent on 01 Nov, 2020
Editor invited
On 31 Oct, 2020
Editor assigned
On 31 Oct, 2020
Submission checks complete
On 31 Oct, 2020
No comments provided
Review #2 received
Received 02 Oct, 2020
Editorial decision: Major Revision
On 02 Oct, 2020
Review #1 received
Received 17 Aug, 2020
Reviewer #2 agreed
On 11 Aug, 2020
Reviewer #1 agreed
On 10 Aug, 2020
Reviewers invited
Invitations sent on 09 Aug, 2020
Editor assigned
On 08 Aug, 2020
First submitted
On 07 Aug, 2020
Submission checks complete
On 07 Aug, 2020
Editor invited
On 07 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Parasites & Vectors.
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.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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