Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides

Summary: Indole is a molecule proposed to be involved in bacterial signaling. We find that indole secretion is induced by sublethal tobramycin concentrations and increases persistence to aminoglycosides in V. cholerae. Indole transcriptomics showed increased expression of raiA, a ribosome associated...

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Main Authors: Manon Lang, Evelyne Krin, Chloé Korlowski, Odile Sismeiro, Hugo Varet, Jean-Yves Coppée, Didier Mazel, Zeynep Baharoglu
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221010968
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author Manon Lang
Evelyne Krin
Chloé Korlowski
Odile Sismeiro
Hugo Varet
Jean-Yves Coppée
Didier Mazel
Zeynep Baharoglu
author_facet Manon Lang
Evelyne Krin
Chloé Korlowski
Odile Sismeiro
Hugo Varet
Jean-Yves Coppée
Didier Mazel
Zeynep Baharoglu
author_sort Manon Lang
collection DOAJ
description Summary: Indole is a molecule proposed to be involved in bacterial signaling. We find that indole secretion is induced by sublethal tobramycin concentrations and increases persistence to aminoglycosides in V. cholerae. Indole transcriptomics showed increased expression of raiA, a ribosome associated factor. Deletion of raiA abolishes the appearance of indole dependent persisters to aminoglycosides, although its overexpression leads to 100-fold increase of persisters, and a reduction in lag phase, evocative of increased active 70S ribosome content, confirmed by sucrose gradient analysis. We propose that, under stress conditions, RaiA-bound inactive 70S ribosomes are stored as “sleeping ribosomes”, and are rapidly reactivated upon stress relief. Our results point to an active process of persister formation through ribosome protection during translational stress (e.g., aminoglycoside treatment) and reactivation upon antibiotic removal. Translation is a universal process, and these results could help elucidate a mechanism of persistence formation in a controlled, thus inducible way.
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spelling doaj.art-784da69c8c9d4db98a7208901f9df3882022-12-21T19:12:52ZengElsevieriScience2589-00422021-10-012410103128Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosidesManon Lang0Evelyne Krin1Chloé Korlowski2Odile Sismeiro3Hugo Varet4Jean-Yves Coppée5Didier Mazel6Zeynep Baharoglu7Département Génomes et Génétique, Institut Pasteur, UMR3525, CNRS, Unité Plasticité du Génome Bactérien, 75015 Paris, France; Sorbonne Université, Collège Doctoral, 75005 Paris, FranceDépartement Génomes et Génétique, Institut Pasteur, UMR3525, CNRS, Unité Plasticité du Génome Bactérien, 75015 Paris, FranceDépartement Génomes et Génétique, Institut Pasteur, UMR3525, CNRS, Unité Plasticité du Génome Bactérien, 75015 Paris, FranceBiomics Technological Platform, Center for Technological Resources and Research, Institut Pasteur, 75015 Paris, FranceBiomics Technological Platform, Center for Technological Resources and Research, Institut Pasteur, 75015 Paris, France; Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, 75015 Paris, FranceBiomics Technological Platform, Center for Technological Resources and Research, Institut Pasteur, 75015 Paris, FranceDépartement Génomes et Génétique, Institut Pasteur, UMR3525, CNRS, Unité Plasticité du Génome Bactérien, 75015 Paris, France; Corresponding authorDépartement Génomes et Génétique, Institut Pasteur, UMR3525, CNRS, Unité Plasticité du Génome Bactérien, 75015 Paris, France; Corresponding authorSummary: Indole is a molecule proposed to be involved in bacterial signaling. We find that indole secretion is induced by sublethal tobramycin concentrations and increases persistence to aminoglycosides in V. cholerae. Indole transcriptomics showed increased expression of raiA, a ribosome associated factor. Deletion of raiA abolishes the appearance of indole dependent persisters to aminoglycosides, although its overexpression leads to 100-fold increase of persisters, and a reduction in lag phase, evocative of increased active 70S ribosome content, confirmed by sucrose gradient analysis. We propose that, under stress conditions, RaiA-bound inactive 70S ribosomes are stored as “sleeping ribosomes”, and are rapidly reactivated upon stress relief. Our results point to an active process of persister formation through ribosome protection during translational stress (e.g., aminoglycoside treatment) and reactivation upon antibiotic removal. Translation is a universal process, and these results could help elucidate a mechanism of persistence formation in a controlled, thus inducible way.http://www.sciencedirect.com/science/article/pii/S2589004221010968BacteriologyMicrobial genomicsViral microbiology
spellingShingle Manon Lang
Evelyne Krin
Chloé Korlowski
Odile Sismeiro
Hugo Varet
Jean-Yves Coppée
Didier Mazel
Zeynep Baharoglu
Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
iScience
Bacteriology
Microbial genomics
Viral microbiology
title Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
title_full Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
title_fullStr Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
title_full_unstemmed Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
title_short Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides
title_sort sleeping ribosomes bacterial signaling triggers raia mediated persistence to aminoglycosides
topic Bacteriology
Microbial genomics
Viral microbiology
url http://www.sciencedirect.com/science/article/pii/S2589004221010968
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