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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, M. en_US
dc.contributor.author Berg, M. en_US
dc.contributor.author Caljon, G. en_US
dc.contributor.author De Muylder, G. en_US
dc.contributor.author Cuypers, B. en_US
dc.contributor.author Castillo, D. en_US
dc.contributor.author Maes, I. en_US
dc.contributor.author Orozco, M. D. C. en_US
dc.contributor.author Vanaerschot, M. en_US
dc.contributor.author Dujardin, J. C. en_US
dc.contributor.author Arevalo, J. en_US
dc.date.accessioned 2017-12-18T12:55:43Z
dc.date.available 2017-12-18T12:55:43Z
dc.date.issued 2017 en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0180532 en_US
dc.identifier.other http://lib.itg.be/pdf/itg/2017/2017ponee0180532.pdf en_US
dc.identifier.other 22 pp. en_US
dc.identifier.other 59 en_US
dc.identifier.other ITG-B1B; ITG-BxA; ITG-B10A; DBM; U-MOLPAR; JIF; DOI; PDF; OAJ; E-only; Abstract; DSPACE64 en_US
dc.identifier.uri http://hdl.handle.net/10390/9544
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 alpha 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 English en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/28742826 en_US
dc.subject Leishmania braziliensis en_US
dc.subject Protozoology en_US
dc.subject Life stages en_US
dc.subject Amastigotes en_US
dc.subject Characterization 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 Article-E en_US
dc.citation.issue 7 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.volume 12 en_US
dc.citation.pages e0180532 en_US
dc.citation.abbreviation PLoS ONE en_US


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