Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage
It was recently hypothesized that Leishmania amastigotes could constitute a semi-quiescent stage characterized by low replication and reduced metabolic activity. This concept developed with Leishmania (Leishmania) mexicana and Leishmania (Leishmania) major models might explain numerous clinical and...
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2017
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| author | Marlene Jara Maya Berg Guy Caljon Géraldine De Muylder Bart Cuypers Denis Castillo Ilse Maes María del Carmen Orozco Manu Vanaerschot Jean‐Claude Dujardin Jorge Arévalo |
| author_browse | Bart Cuypers Denis Castillo Guy Caljon Géraldine De Muylder Ilse Maes Jean‐Claude Dujardin Jorge Arévalo Manu Vanaerschot Marlene Jara María del Carmen Orozco Maya Berg |
| author_facet | Marlene Jara Maya Berg Guy Caljon Géraldine De Muylder Bart Cuypers Denis Castillo Ilse Maes María del Carmen Orozco Manu Vanaerschot Jean‐Claude Dujardin Jorge Arévalo |
| author_sort | Marlene Jara |
| collection | Producción científica |
| description | It was recently hypothesized that Leishmania amastigotes could constitute a semi-quiescent stage characterized by low replication and reduced metabolic activity. This concept developed with Leishmania (Leishmania) mexicana and Leishmania (Leishmania) major models might explain numerous clinical and sub-clinical features of Leishmania (Viannia) braziliensis infections, like reactivation of the disease, non-response to chemotherapy or asymptomatic infections. We compared here in vitro the proliferative capability of L. (V.) braziliensis amastigotes and promastigotes, assessed the expression of key molecular parameters and performed metabolomic analysis. We found that contrary to the highly proliferative promastigotes, amastigotes (axenic and intracellular) do not show evidence of extensive proliferation. In parallel, amastigotes showed a significant decrease of (i) the kDNA mini-circle abundance, (ii) the intracellular ATP level, (iii) the ribosomal components: rRNA subunits 18S and 28S α and ribosomal proteins RPS15 and RPL19, (iv) total RNA and protein levels. An untargeted metabolomic study identified clear differences between the different life stages: in comparison to logarithmic promastigotes, axenic amastigotes showed (a) a strong decrease of 14 essential and non-essential amino acids and eight metabolites involved in polyamine synthesis, (b) extensive changes in the phospholipids composition and (c) increased levels of several endogenous and exogenous sterols. Altogether, our results show that L. (V.) braziliensis amastigotes can show a phenotype with negligible rate of proliferation, a lower capacity of biosynthesis, a reduced bio-energetic level and a strongly altered metabolism. Our results pave the way for further exploration of quiescence among amastigotes of this species. |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/939 |
| institution | UPeU |
| language | English |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | oai:cris.upeu.edu.pe:20.500.15037/9392026-10-30T16:15:00ZMacromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stageMarlene JaraMaya BergGuy CaljonGéraldine De MuylderBart CuypersDenis CastilloIlse MaesMaría del Carmen OrozcoManu VanaerschotJean‐Claude DujardinJorge ArévaloAmastigoteLeishmania braziliensisBiologyAxenicLeishmaniaLeishmania mexicanaMetabolomicsMicrobiologyLeishmaniasisCutaneous leishmaniasisGeneticsParasite hostingBioinformaticsComputer scienceWorld Wide WebBacteriaAmastigoteLeishmania braziliensisBiologyAxenicLeishmaniaLeishmania mexicanaMetabolomicsMicrobiologyLeishmaniasisCutaneous leishmaniasisGeneticsParasite hostingBioinformaticsAdenosine Diphosphate metabolismAdenosine Diphosphate metabolismAdenosine Diphosphate metabolismAdenosine Diphosphate metabolismAdenosine Triphosphate metabolismAdenosine Triphosphate metabolismAdenosine Triphosphate metabolismAdenosine Triphosphate metabolismAnimalsAnimalsAnimalsAnimalsCells, CulturedCells, CulturedCells, CulturedCells, CulturedFemaleFemaleFemaleFemaleLeishmania braziliensis growth & developmentLeishmania braziliensis growth & developmentLeishmania braziliensis growth & developmentLeishmania braziliensis growth & developmentLeishmania braziliensis metabolismLeishmania braziliensis metabolismLeishmania braziliensis metabolismLeishmania braziliensis metabolismMice, Inbred BALB CMice, Inbred BALB CMice, Inbred BALB CMice, Inbred BALB CRibosomal Proteins analysisRibosomal Proteins analysisRibosomal Proteins analysisRibosomal Proteins analysisRibosomal Proteins metabolismRibosomal Proteins metabolismRibosomal Proteins metabolismRibosomal Proteins metabolismProtozoan Proteins analysisProtozoan Proteins analysisProtozoan Proteins analysisProtozoan Proteins analysisProtozoan Proteins metabolismProtozoan Proteins metabolismProtozoan Proteins metabolismProtozoan Proteins metabolismRNA, Protozoan analysisRNA, Protozoan analysisRNA, Protozoan analysisRNA, Protozoan analysisRNA, Protozoan metabolismRNA, Protozoan metabolismRNA, Protozoan metabolismRNA, Protozoan metabolismLeishmaniasis, Cutaneous parasitologyLeishmaniasis, Cutaneous parasitologyLeishmaniasis, Cutaneous parasitologyLeishmaniasis, Cutaneous parasitologyBiosynthetic PathwaysBiosynthetic PathwaysBiosynthetic PathwaysBiosynthetic PathwaysMetabolomeMetabolomeMetabolomeMetabolomeHealth Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis StudiesHealth Sciences Medicine Epidemiology Trypanosoma species research and implicationsLife Sciences Agricultural and Biological Sciences Plant Science Insect Pest Control StrategiesIt was recently hypothesized that Leishmania amastigotes could constitute a semi-quiescent stage characterized by low replication and reduced metabolic activity. This concept developed with Leishmania (Leishmania) mexicana and Leishmania (Leishmania) major models might explain numerous clinical and sub-clinical features of Leishmania (Viannia) braziliensis infections, like reactivation of the disease, non-response to chemotherapy or asymptomatic infections. We compared here in vitro the proliferative capability of L. (V.) braziliensis amastigotes and promastigotes, assessed the expression of key molecular parameters and performed metabolomic analysis. We found that contrary to the highly proliferative promastigotes, amastigotes (axenic and intracellular) do not show evidence of extensive proliferation. In parallel, amastigotes showed a significant decrease of (i) the kDNA mini-circle abundance, (ii) the intracellular ATP level, (iii) the ribosomal components: rRNA subunits 18S and 28S α and ribosomal proteins RPS15 and RPL19, (iv) total RNA and protein levels. An untargeted metabolomic study identified clear differences between the different life stages: in comparison to logarithmic promastigotes, axenic amastigotes showed (a) a strong decrease of 14 essential and non-essential amino acids and eight metabolites involved in polyamine synthesis, (b) extensive changes in the phospholipids composition and (c) increased levels of several endogenous and exogenous sterols. Altogether, our results show that L. (V.) braziliensis amastigotes can show a phenotype with negligible rate of proliferation, a lower capacity of biosynthesis, a reduced bio-energetic level and a strongly altered metabolism. Our results pave the way for further exploration of quiescence among amastigotes of this species.Articlehttps://pubmed.ncbi.nlm.nih.gov/28742826https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0180532&type=printablehttps://doi.org/10.1371/journal.pone.018053210.1371/journal.pone.0180532https://hdl.handle.net/20.500.15037/939W2738372057enPLoS ONE1932-62032017-07-252026-06-13T09:40:59Z2026-06-13T09:40:59Z |
| spellingShingle | Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Computer science World Wide Web Bacteria Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Animals Animals Animals Animals Cells, Cultured Cells, Cultured Cells, Cultured Cells, Cultured Female Female Female Female Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Metabolome Metabolome Metabolome Metabolome Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Plant Science Insect Pest Control Strategies Marlene Jara Maya Berg Guy Caljon Géraldine De Muylder Bart Cuypers Denis Castillo Ilse Maes María del Carmen Orozco Manu Vanaerschot Jean‐Claude Dujardin Jorge Arévalo Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title | Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title_full | Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title_fullStr | Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title_full_unstemmed | Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title_short | Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage |
| title_sort | macromolecular biosynthetic parameters and metabolic profile in different life stages of leishmania braziliensis amastigotes as a functionally less active stage |
| topic | Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Computer science World Wide Web Bacteria Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Animals Animals Animals Animals Cells, Cultured Cells, Cultured Cells, Cultured Cells, Cultured Female Female Female Female Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Metabolome Metabolome Metabolome Metabolome Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Plant Science Insect Pest Control Strategies |
| topic_facet | Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Computer science World Wide Web Bacteria Amastigote Leishmania braziliensis Biology Axenic Leishmania Leishmania mexicana Metabolomics Microbiology Leishmaniasis Cutaneous leishmaniasis Genetics Parasite hosting Bioinformatics Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Diphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Adenosine Triphosphate metabolism Animals Animals Animals Animals Cells, Cultured Cells, Cultured Cells, Cultured Cells, Cultured Female Female Female Female Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis growth & development Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Leishmania braziliensis metabolism Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Mice, Inbred BALB C Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins analysis Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Ribosomal Proteins metabolism Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins analysis Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism Protozoan Proteins metabolism RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan analysis RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism RNA, Protozoan metabolism Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Biosynthetic Pathways Metabolome Metabolome Metabolome Metabolome Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Plant Science Insect Pest Control Strategies |
| url | https://pubmed.ncbi.nlm.nih.gov/28742826 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0180532&type=printable https://doi.org/10.1371/journal.pone.0180532 https://hdl.handle.net/20.500.15037/939 |
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