Universidad Peruana Cayetano Heredia

Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage

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dc.contributor.author Jara, Marlene
dc.contributor.author Berg, Maya
dc.contributor.author Caljon, Guy
dc.contributor.author de Muylder, Geraldine
dc.contributor.author Cuypers, Bart
dc.contributor.author Castillo Pareja, Denis Helan
dc.contributor.author Maes, Ilse
dc.contributor.author Orozco, María Del Carmen
dc.contributor.author Vanaerschot, Manu
dc.contributor.author Dujardin, Jean-Claude
dc.contributor.author Arévalo Zelada, Jorge Luis
dc.date.accessioned 2019-01-25T15:28:05Z
dc.date.available 2019-01-25T15:28:05Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4696
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS ONE
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Metabolome en_US
dc.subject Adenosine Diphosphate/metabolism en_US
dc.subject Adenosine Triphosphate/metabolism en_US
dc.subject Animals en_US
dc.subject Biosynthetic Pathways en_US
dc.subject Cells, Cultured en_US
dc.subject Female en_US
dc.subject Leishmania braziliensis/growth & development/metabolism en_US
dc.subject Leishmaniasis, Cutaneous/parasitology en_US
dc.subject Mice, Inbred BALB C en_US
dc.subject Protozoan Proteins/analysis/metabolism en_US
dc.subject Ribosomal Proteins/analysis/metabolism en_US
dc.subject RNA, Protozoan/analysis/metabolism en_US
dc.title Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pone.0180532
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 1932-6203


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