| Author | Crepaldi, Frederico | |
| Author | Toledo, Juliano Simões de | |
| Author | armo, Anderson Oliveira do C. | |
| Author | Machado, Leopoldo Ferreira Marques | |
| Author | Brito, Daniela Diniz Viana de | |
| Author | Serufo, Angela Vieira | |
| Author | Almeida, Ana Paula Martins | |
| Author | Oliveira, Leandro Gonzaga de | |
| Author | Ricotta, Tiago Queiroga Nery | |
| Author | Moreira, Douglas de Souza | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | Diniz, Ariane Barros | |
| Author | Menezes, Gustavo Batista | |
| Author | López-Gonzálvez, Ángeles | |
| Author | Barbas, Coral | |
| Author | Fernandes, Ana Paula | |
| Access date | 2020-02-04T17:13:46Z | |
| Available date | 2020-02-04T17:13:46Z | |
| Document date | 2019 | |
| Citation | 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. | pt_BR |
| ISSN | 2235-2988 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/39723 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media SA | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | L. amazonensis | pt_BR |
| Title | Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.3389/fcimb.2019.00403 | |
| Abstract | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Laboratório de Biotecnologia e Marcadores Moleculares. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Manchester Institute of Biotechnology. The University of Manchester. Manchester, United Kingdom. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain. | pt_BR |
| Affilliation | Centro de Metabolómica y Bioanálisis. Unidad Metabolómica. Interacciones y Bioanálisis (UMIB), Universidad CEU. San Pablo, Boadilla del Monte, Spain. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brasil. | pt_BR |
| Subject | L. amazonensis | pt_BR |
| Subject | Attenuation | pt_BR |
| Subject | Inflammation | pt_BR |
| Subject | Metabolic pathways | pt_BR |
| Subject | Metacyclogenesis | pt_BR |
| Subject | Multiplatform metabolomic fingerprint | pt_BR |
