Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models

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...

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Main Authors: Marlene Jara, Michael Barrett, Ilse Maes, Clement Regnault, Hideo Imamura, Malgorzata Anna Domagalska, Jean-Claude Dujardin
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/10/1/97
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author Marlene Jara
Michael Barrett
Ilse Maes
Clement Regnault
Hideo Imamura
Malgorzata Anna Domagalska
Jean-Claude Dujardin
author_facet Marlene Jara
Michael Barrett
Ilse Maes
Clement Regnault
Hideo Imamura
Malgorzata Anna Domagalska
Jean-Claude Dujardin
author_sort Marlene Jara
collection DOAJ
description 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 <i>Leishmania</i>, 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 <i>Leishmania</i> 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.
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spelling doaj.art-809464636c7843c9bc3abaea955916452023-11-23T14:47:17ZengMDPI AGMicroorganisms2076-26072022-01-011019710.3390/microorganisms10010097Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as ModelsMarlene Jara0Michael Barrett1Ilse Maes2Clement Regnault3Hideo Imamura4Malgorzata Anna Domagalska5Jean-Claude Dujardin6Molecular Parasitology Unit, Institute of Tropical Medicine Antwerp, 2000 Antwerp, BelgiumWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKMolecular Parasitology Unit, Institute of Tropical Medicine Antwerp, 2000 Antwerp, BelgiumWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKCentre for Medical Genetics, Universitair Ziekenhuis Brussel, 1090 Brussels, BelgiumMolecular Parasitology Unit, Institute of Tropical Medicine Antwerp, 2000 Antwerp, BelgiumMolecular Parasitology Unit, Institute of Tropical Medicine Antwerp, 2000 Antwerp, BelgiumMicroorganisms 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 <i>Leishmania</i>, 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 <i>Leishmania</i> 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.https://www.mdpi.com/2076-2607/10/1/97<i>Leishmania</i>quiescencedrug pressure
spellingShingle Marlene Jara
Michael Barrett
Ilse Maes
Clement Regnault
Hideo Imamura
Malgorzata Anna Domagalska
Jean-Claude Dujardin
Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
Microorganisms
<i>Leishmania</i>
quiescence
drug pressure
title Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
title_full Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
title_fullStr Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
title_full_unstemmed Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
title_short Transcriptional Shift and Metabolic Adaptations during <i>Leishmania</i> Quiescence Using Stationary Phase and Drug Pressure as Models
title_sort transcriptional shift and metabolic adaptations during i leishmania i quiescence using stationary phase and drug pressure as models
topic <i>Leishmania</i>
quiescence
drug pressure
url https://www.mdpi.com/2076-2607/10/1/97
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