Cargando...
Macromolecular biosynthetic parameters and metabolic profile in different life stages of Leishmania braziliensis: Amastigotes as a functionally less active stage
Author(s)
Universidad Peruana Cayetano Heredia
Maya Berg
Instituut voor Tropische Geneeskunde
Guy Caljon
Instituut voor Tropische Geneeskunde
Géraldine De Muylder
Instituut voor Tropische Geneeskunde
Bart Cuypers
University of Antwerp
Denis Castillo
Universidad Peruana Cayetano Heredia
Ilse Maes
Instituut voor Tropische Geneeskunde
María del Carmen Orozco
Universidad Peruana Cayetano Heredia
Manu Vanaerschot
Instituut voor Tropische Geneeskunde
Jean‐Claude Dujardin
University of Antwerp
Jorge Arévalo
Universidad Peruana Cayetano Heredia
Date Issued
25 de julio de 2017
Type
Article
Volume
12
Issue
7
Series/Report No.
PLoS ONE
Start Page
e0180532
End Page
e0180532
ISSN
1932-6203
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.
Keywords