Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/39723 |
Resumo: | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil / Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain. |
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Crepaldi, FredericoToledo, Juliano Simões dearmo, Anderson Oliveira do C.Machado, Leopoldo Ferreira MarquesBrito, Daniela Diniz Viana deSerufo, Angela VieiraAlmeida, Ana Paula MartinsOliveira, Leandro Gonzaga deRicotta, Tiago Queiroga NeryMoreira, Douglas de SouzaMurta, Silvane Maria FonsecaDiniz, Ariane BarrosMenezes, Gustavo BatistaLópez-Gonzálvez, ÁngelesBarbas, CoralFernandes, Ana Paula2020-02-04T17:13:46Z2020-02-04T17:13:46Z2019CREPALDI, Frederico et al. Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach. Frontiers in Cellular and Infection Microbiology, v. 9, p. 1-22, 4 Dec. 2019.2235-2988https://www.arca.fiocruz.br/handle/icict/3972310.3389/fcimb.2019.00403engFrontiers Media SAL. amazonensisL. amazonensisAttenuationInflammationMetabolic pathwaysMetacyclogenesisMultiplatform metabolomic fingerprintMapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approachinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil / Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil / Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Laboratório de Biotecnologia e Marcadores Moleculares. Belo Horizonte, MG, Brasil.Manchester Institute of Biotechnology. The University of Manchester. Manchester, United Kingdom.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain.Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain.Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil.Leishmaniases are widespread neglected diseases with an incidence of 1.6 million new cases and 40 thousand deaths per year. Leishmania parasites may show distinct, species-specific patterns of virulence that lead to different clinical manifestations. It is well known that successive in vitro passages (SIVP) lead to the attenuation of virulence, but neither the metabolism nor the pathways involved in these processes are well understood. Herein, promastigotes of a virulent L. amazonensis strain recently isolated from mice was compared to SIVP derived and attenuated promastigotes, submitted to 10, 40, and 60 axenic passages and named R10, R40, and R60, respectively. In vitro assays and in vivo tests were performed to characterize and confirmed the attenuation profiles. A metabolomic fingerprint comparison of R0, R10, and R60 was performed by means of capillary electrophoresis, liquid and gas chromatography coupled to mass spectrometry. To validate the metabolomic data, qPCR for selected loci, flow cytometry to measure aPS exposure, sensitivity to antimony tartrate and ROS production assays were conducted. The 65 identified metabolites were clustered in biochemical categories and mapped in eight metabolic pathways: ABC transporters; fatty acid biosynthesis; glycine, serine and threonine metabolism; β-alanine metabolism; glutathione metabolism; oxidative phosphorylation; glycerophospholipid metabolism and lysine degradation. The obtained metabolomic data correlated with previous proteomic findings of the SVIP parasites and the gene expression of 13 selected targets. Late SIVP cultures were more sensitive to SbIII produced more ROS and exposed less phosphatidylserine in their surface. The correspondent pathways were connected to build a biochemical map of the most significant alterations involved with the process of attenuation of L. amazonensis. Overall, the reported data pointed out to a very dynamic and continuous metabolic reprogramming process, accompanied by changes in energetic, lipid and redox metabolisms, membrane remodeling and reshaping of parasite-host cells interactions, causing impacts in chemotaxis, host inflammatory responses and infectivity at the early stages of infection.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/39723/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALMapping Alterations Induced .pdfMapping Alterations Induced .pdfapplication/pdf15523213https://www.arca.fiocruz.br/bitstream/icict/39723/2/Mapping%20Alterations%20Induced%20.pdfa485f8b44283ace87e344a06f1a2edeaMD52TEXTMapping Alterations Induced .pdf.txtMapping Alterations Induced .pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
title |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
spellingShingle |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach Crepaldi, Frederico L. amazonensis L. amazonensis Attenuation Inflammation Metabolic pathways Metacyclogenesis Multiplatform metabolomic fingerprint |
title_short |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
title_full |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
title_fullStr |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
title_full_unstemmed |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
title_sort |
Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach |
author |
Crepaldi, Frederico |
author_facet |
Crepaldi, Frederico Toledo, Juliano Simões de armo, Anderson Oliveira do C. Machado, Leopoldo Ferreira Marques Brito, Daniela Diniz Viana de Serufo, Angela Vieira Almeida, Ana Paula Martins Oliveira, Leandro Gonzaga de Ricotta, Tiago Queiroga Nery Moreira, Douglas de Souza Murta, Silvane Maria Fonseca Diniz, Ariane Barros Menezes, Gustavo Batista López-Gonzálvez, Ángeles Barbas, Coral Fernandes, Ana Paula |
author_role |
author |
author2 |
Toledo, Juliano Simões de armo, Anderson Oliveira do C. Machado, Leopoldo Ferreira Marques Brito, Daniela Diniz Viana de Serufo, Angela Vieira Almeida, Ana Paula Martins Oliveira, Leandro Gonzaga de Ricotta, Tiago Queiroga Nery Moreira, Douglas de Souza Murta, Silvane Maria Fonseca Diniz, Ariane Barros Menezes, Gustavo Batista López-Gonzálvez, Ángeles Barbas, Coral Fernandes, Ana Paula |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Crepaldi, Frederico Toledo, Juliano Simões de armo, Anderson Oliveira do C. Machado, Leopoldo Ferreira Marques Brito, Daniela Diniz Viana de Serufo, Angela Vieira Almeida, Ana Paula Martins Oliveira, Leandro Gonzaga de Ricotta, Tiago Queiroga Nery Moreira, Douglas de Souza Murta, Silvane Maria Fonseca Diniz, Ariane Barros Menezes, Gustavo Batista López-Gonzálvez, Ángeles Barbas, Coral Fernandes, Ana Paula |
dc.subject.other.pt_BR.fl_str_mv |
L. amazonensis |
topic |
L. amazonensis L. amazonensis Attenuation Inflammation Metabolic pathways Metacyclogenesis Multiplatform metabolomic fingerprint |
dc.subject.en.pt_BR.fl_str_mv |
L. amazonensis Attenuation Inflammation Metabolic pathways Metacyclogenesis Multiplatform metabolomic fingerprint |
description |
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil / Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-02-04T17:13:46Z |
dc.date.available.fl_str_mv |
2020-02-04T17:13:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
CREPALDI, Frederico et al. Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach. Frontiers in Cellular and Infection Microbiology, v. 9, p. 1-22, 4 Dec. 2019. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/39723 |
dc.identifier.issn.pt_BR.fl_str_mv |
2235-2988 |
dc.identifier.doi.none.fl_str_mv |
10.3389/fcimb.2019.00403 |
identifier_str_mv |
CREPALDI, Frederico et al. Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach. Frontiers in Cellular and Infection Microbiology, v. 9, p. 1-22, 4 Dec. 2019. 2235-2988 10.3389/fcimb.2019.00403 |
url |
https://www.arca.fiocruz.br/handle/icict/39723 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media SA |
publisher.none.fl_str_mv |
Frontiers Media SA |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Fundação Oswaldo Cruz (FIOCRUZ) |
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FIOCRUZ |
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FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
collection |
Repositório Institucional da FIOCRUZ (ARCA) |
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