Transcriptional shift and metabolic adaptations during Leishmania quiescence using stationary phase and drug pressure as models

Jara, M., Barrett, M. , Maes, I., Regnault, C., Imamura, H., Domagalska, M. A. and Dujardin, J.-C. (2022) Transcriptional shift and metabolic adaptations during Leishmania quiescence using stationary phase and drug pressure as models. Microorganisms, 10(1), 97. (doi: 10.3390/microorganisms10010097) (PMID:35056546) (PMCID:PMC8781126)

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Abstract

Microorganisms can adopt a quiescent physiological condition which acts as a survival strategy under unfavorable conditions. Quiescent cells are characterized by slow or non-proliferation and a deep downregulation of processes related to biosynthesis. Although quiescence has been described mostly in bacteria, this survival skill is widespread, including in eukaryotic microorganisms. In Leishmania, a digenetic parasitic protozoan that causes a major infectious disease, quiescence has been demonstrated, but the molecular and metabolic features enabling its maintenance are unknown. Here, we quantified the transcriptome and metabolome of Leishmania promastigotes and amastigotes where quiescence was induced in vitro either, through drug pressure or by stationary phase. Quiescent cells have a global and coordinated reduction in overall transcription, with levels dropping to as low as 0.4% of those in proliferating cells. However, a subset of transcripts did not follow this trend and were relatively upregulated in quiescent populations, including those encoding membrane components, such as amastins and GP63, or processes like autophagy. The metabolome followed a similar trend of overall downregulation albeit to a lesser magnitude than the transcriptome. It is noteworthy that among the commonly upregulated metabolites were those involved in carbon sources as an alternative to glucose. This first integrated two omics layers afford novel insight into cell regulation and show commonly modulated features across stimuli and stages.

Item Type:Articles
Additional Information:This study was financially supported by the Flemish Fund for Scientific Research (postdoctoral grant to MJ, FWO-1223420N). This study was also supported by Flemish Ministry of Science and Innovation (SOFI481 Grants SINGLE and MADLEI. MPB was funded as part of the Wellcome Trust core grant to the Wellcome Centre for Integrative Parasitology (grant 104111/Z/14/Z).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Regnault, Mr Clement and Barrett, Professor Michael
Creator Roles:
Barrett, M.Resources, Writing – review and editing
Regnault, C.Software, Formal analysis, Data curation
Authors: Jara, M., Barrett, M., Maes, I., Regnault, C., Imamura, H., Domagalska, M. A., and Dujardin, J.-C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Microorganisms
Publisher:MDPI
ISSN:2076-2607
ISSN (Online):2076-2607
Published Online:03 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Microorganisms 10(1): 97
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology