Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines
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-I...
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| Veröffentlicht in: | Parasites & vectors 2020-11, Vol.13 (1), p.1-600, Article 600 |
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| creator | Andrade, Juvana Moreira Goncalves, Leilane Oliveira Liarte, Daniel Barbosa Lima, Davi Alvarenga Guimaraes, Frederico Goncalves de Melo Resende, Daniela Santi, Ana Maria Murta de Oliveira, Luciana Marcia Velloso, Joao Paulo Linhares Delfino, Renato Guimaraes Pescher, Pascale Spath, Gerald F. Ruiz, Jeronimo Conceicao Murta, Silvane Maria Fonseca |
| description | 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. |
| doi_str_mv | 10.1186/s13071-020-04486-4 |
| format | Article |
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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.</description><identifier>ISSN: 1756-3305</identifier><identifier>EISSN: 1756-3305</identifier><identifier>DOI: 10.1186/s13071-020-04486-4</identifier><identifier>PMID: 33256787</identifier><language>eng</language><publisher>LONDON: Springer Nature</publisher><subject>Annotations ; Antimony ; Biogenesis ; Biological activity ; Chemical properties ; Chemotherapy ; Complementary DNA ; Deoxyribonucleic acid ; Differentially expressed genes ; DNA ; Drug resistance ; Drug resistance in microorganisms ; Drug therapy ; Gene expression ; Gene mapping ; Gene sequencing ; Genes ; Genetic aspects ; Genomes ; Health aspects ; Host-parasite interactions ; Leishmania ; Leishmania infantum ; Leishmaniasis ; Life Sciences ; Life Sciences & Biomedicine ; Metabolic pathways ; Microbiology and Parasitology ; Nucleic acids ; Nucleotide sequence ; Parasites ; Parasitic diseases ; Parasitological research ; Parasitology ; Phenotypes ; Phosphorylation ; Physiological aspects ; Potassium ; Potassium antimonyl tartrate ; Proteins ; Resistance ; Resistance mechanisms ; Ribosomes ; RNA ; RNA processing ; RNA sequencing ; rRNA ; Science & Technology ; Software ; Statistical analysis ; Statistical methods ; Submarine pipelines ; Transcriptome ; Transcriptomics ; Trivalent antimony ; Tropical Medicine ; Ubiquitination ; Vector-borne diseases</subject><ispartof>Parasites & vectors, 2020-11, Vol.13 (1), p.1-600, Article 600</ispartof><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>18</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000596393000002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c612t-804072f7a449566b78b9f0996516f7c9847ec859d8495ca11d88058c088cf7f63</citedby><cites>FETCH-LOGICAL-c612t-804072f7a449566b78b9f0996516f7c9847ec859d8495ca11d88058c088cf7f63</cites><orcidid>0000-0002-1000-2339 ; 0000-0002-8523-2155 ; 0000-0003-2796-7855 ; 0000-0002-0256-2029</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706067/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706067/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,28253,53796,53798</link.rule.ids><backlink>$$Uhttps://pasteur.hal.science/pasteur-03109036$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrade, Juvana Moreira</creatorcontrib><creatorcontrib>Goncalves, Leilane Oliveira</creatorcontrib><creatorcontrib>Liarte, Daniel Barbosa</creatorcontrib><creatorcontrib>Lima, Davi Alvarenga</creatorcontrib><creatorcontrib>Guimaraes, Frederico Goncalves</creatorcontrib><creatorcontrib>de Melo Resende, Daniela</creatorcontrib><creatorcontrib>Santi, Ana Maria Murta</creatorcontrib><creatorcontrib>de Oliveira, Luciana Marcia</creatorcontrib><creatorcontrib>Velloso, Joao Paulo Linhares</creatorcontrib><creatorcontrib>Delfino, Renato Guimaraes</creatorcontrib><creatorcontrib>Pescher, Pascale</creatorcontrib><creatorcontrib>Spath, Gerald F.</creatorcontrib><creatorcontrib>Ruiz, Jeronimo Conceicao</creatorcontrib><creatorcontrib>Murta, Silvane Maria Fonseca</creatorcontrib><title>Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines</title><title>Parasites & vectors</title><addtitle>PARASITE VECTOR</addtitle><description>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.</description><subject>Annotations</subject><subject>Antimony</subject><subject>Biogenesis</subject><subject>Biological activity</subject><subject>Chemical properties</subject><subject>Chemotherapy</subject><subject>Complementary DNA</subject><subject>Deoxyribonucleic acid</subject><subject>Differentially expressed genes</subject><subject>DNA</subject><subject>Drug resistance</subject><subject>Drug resistance in microorganisms</subject><subject>Drug therapy</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Host-parasite interactions</subject><subject>Leishmania</subject><subject>Leishmania infantum</subject><subject>Leishmaniasis</subject><subject>Life Sciences</subject><subject>Life Sciences & Biomedicine</subject><subject>Metabolic pathways</subject><subject>Microbiology and Parasitology</subject><subject>Nucleic acids</subject><subject>Nucleotide sequence</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Parasitological research</subject><subject>Parasitology</subject><subject>Phenotypes</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Potassium</subject><subject>Potassium antimonyl tartrate</subject><subject>Proteins</subject><subject>Resistance</subject><subject>Resistance mechanisms</subject><subject>Ribosomes</subject><subject>RNA</subject><subject>RNA processing</subject><subject>RNA sequencing</subject><subject>rRNA</subject><subject>Science & Technology</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Submarine pipelines</subject><subject>Transcriptome</subject><subject>Transcriptomics</subject><subject>Trivalent antimony</subject><subject>Tropical Medicine</subject><subject>Ubiquitination</subject><subject>Vector-borne 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Juvana Moreira</creator><creator>Goncalves, Leilane Oliveira</creator><creator>Liarte, Daniel Barbosa</creator><creator>Lima, Davi Alvarenga</creator><creator>Guimaraes, Frederico Goncalves</creator><creator>de Melo Resende, Daniela</creator><creator>Santi, Ana Maria Murta</creator><creator>de Oliveira, Luciana Marcia</creator><creator>Velloso, Joao Paulo Linhares</creator><creator>Delfino, Renato Guimaraes</creator><creator>Pescher, Pascale</creator><creator>Spath, Gerald F.</creator><creator>Ruiz, Jeronimo Conceicao</creator><creator>Murta, Silvane Maria Fonseca</creator><general>Springer Nature</general><general>BioMed Central Ltd</general><general>BioMed 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transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines</title><author>Andrade, Juvana Moreira ; Goncalves, Leilane Oliveira ; Liarte, Daniel Barbosa ; Lima, Davi Alvarenga ; Guimaraes, Frederico Goncalves ; de Melo Resende, Daniela ; Santi, Ana Maria Murta ; de Oliveira, Luciana Marcia ; Velloso, Joao Paulo Linhares ; Delfino, Renato Guimaraes ; Pescher, Pascale ; Spath, Gerald F. ; Ruiz, Jeronimo Conceicao ; Murta, Silvane Maria Fonseca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c612t-804072f7a449566b78b9f0996516f7c9847ec859d8495ca11d88058c088cf7f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Annotations</topic><topic>Antimony</topic><topic>Biogenesis</topic><topic>Biological activity</topic><topic>Chemical properties</topic><topic>Chemotherapy</topic><topic>Complementary DNA</topic><topic>Deoxyribonucleic acid</topic><topic>Differentially expressed genes</topic><topic>DNA</topic><topic>Drug resistance</topic><topic>Drug resistance in microorganisms</topic><topic>Drug therapy</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Host-parasite interactions</topic><topic>Leishmania</topic><topic>Leishmania infantum</topic><topic>Leishmaniasis</topic><topic>Life Sciences</topic><topic>Life Sciences & Biomedicine</topic><topic>Metabolic pathways</topic><topic>Microbiology and Parasitology</topic><topic>Nucleic acids</topic><topic>Nucleotide sequence</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Parasitological research</topic><topic>Parasitology</topic><topic>Phenotypes</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Potassium</topic><topic>Potassium antimonyl tartrate</topic><topic>Proteins</topic><topic>Resistance</topic><topic>Resistance mechanisms</topic><topic>Ribosomes</topic><topic>RNA</topic><topic>RNA processing</topic><topic>RNA sequencing</topic><topic>rRNA</topic><topic>Science & Technology</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Submarine pipelines</topic><topic>Transcriptome</topic><topic>Transcriptomics</topic><topic>Trivalent antimony</topic><topic>Tropical Medicine</topic><topic>Ubiquitination</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andrade, Juvana Moreira</creatorcontrib><creatorcontrib>Goncalves, Leilane Oliveira</creatorcontrib><creatorcontrib>Liarte, Daniel Barbosa</creatorcontrib><creatorcontrib>Lima, Davi Alvarenga</creatorcontrib><creatorcontrib>Guimaraes, Frederico Goncalves</creatorcontrib><creatorcontrib>de Melo Resende, Daniela</creatorcontrib><creatorcontrib>Santi, Ana Maria Murta</creatorcontrib><creatorcontrib>de Oliveira, Luciana Marcia</creatorcontrib><creatorcontrib>Velloso, Joao Paulo Linhares</creatorcontrib><creatorcontrib>Delfino, Renato Guimaraes</creatorcontrib><creatorcontrib>Pescher, Pascale</creatorcontrib><creatorcontrib>Spath, Gerald F.</creatorcontrib><creatorcontrib>Ruiz, Jeronimo Conceicao</creatorcontrib><creatorcontrib>Murta, Silvane Maria Fonseca</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andrade, Juvana Moreira</au><au>Goncalves, Leilane Oliveira</au><au>Liarte, Daniel Barbosa</au><au>Lima, Davi Alvarenga</au><au>Guimaraes, Frederico Goncalves</au><au>de Melo Resende, Daniela</au><au>Santi, Ana Maria Murta</au><au>de Oliveira, Luciana Marcia</au><au>Velloso, Joao Paulo Linhares</au><au>Delfino, Renato Guimaraes</au><au>Pescher, Pascale</au><au>Spath, Gerald F.</au><au>Ruiz, Jeronimo Conceicao</au><au>Murta, Silvane Maria Fonseca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines</atitle><jtitle>Parasites & vectors</jtitle><stitle>PARASITE VECTOR</stitle><date>2020-11-30</date><risdate>2020</risdate><volume>13</volume><issue>1</issue><spage>1</spage><epage>600</epage><pages>1-600</pages><artnum>600</artnum><issn>1756-3305</issn><eissn>1756-3305</eissn><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.</abstract><cop>LONDON</cop><pub>Springer Nature</pub><pmid>33256787</pmid><doi>10.1186/s13071-020-04486-4</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1000-2339</orcidid><orcidid>https://orcid.org/0000-0002-8523-2155</orcidid><orcidid>https://orcid.org/0000-0003-2796-7855</orcidid><orcidid>https://orcid.org/0000-0002-0256-2029</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1756-3305 |
| ispartof | Parasites & vectors, 2020-11, Vol.13 (1), p.1-600, Article 600 |
| issn | 1756-3305 1756-3305 |
| language | eng |
| recordid | cdi_gale_infotracacademiconefile_A650638428 |
| source | DOAJ Directory of Open Access Journals; SpringerNature Journals; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central; Springer Nature OA/Free Journals |
| subjects | Annotations Antimony Biogenesis Biological activity Chemical properties Chemotherapy Complementary DNA Deoxyribonucleic acid Differentially expressed genes DNA Drug resistance Drug resistance in microorganisms Drug therapy Gene expression Gene mapping Gene sequencing Genes Genetic aspects Genomes Health aspects Host-parasite interactions Leishmania Leishmania infantum Leishmaniasis Life Sciences Life Sciences & Biomedicine Metabolic pathways Microbiology and Parasitology Nucleic acids Nucleotide sequence Parasites Parasitic diseases Parasitological research Parasitology Phenotypes Phosphorylation Physiological aspects Potassium Potassium antimonyl tartrate Proteins Resistance Resistance mechanisms Ribosomes RNA RNA processing RNA sequencing rRNA Science & Technology Software Statistical analysis Statistical methods Submarine pipelines Transcriptome Transcriptomics Trivalent antimony Tropical Medicine Ubiquitination Vector-borne diseases |
| title | Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T17%3A19%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparative%20transcriptomic%20analysis%20of%20antimony%20resistant%20and%20susceptible%20Leishmania%20infantum%20lines&rft.jtitle=Parasites%20&%20vectors&rft.au=Andrade,%20Juvana%20Moreira&rft.date=2020-11-30&rft.volume=13&rft.issue=1&rft.spage=1&rft.epage=600&rft.pages=1-600&rft.artnum=600&rft.issn=1756-3305&rft.eissn=1756-3305&rft_id=info:doi/10.1186/s13071-020-04486-4&rft_dat=%3Cgale_proqu%3EA650638428%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471216414&rft_id=info:pmid/33256787&rft_galeid=A650638428&rft_doaj_id=oai_doaj_org_article_13a32cf789e24844b64842b797114098&rfr_iscdi=true |