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The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage
Bacterial populations harbor a small fraction of cells that display transient multidrug tolerance. These so-called persister cells are extremely difficult to eradicate and contribute to the recalcitrance of chronic infections. Several signaling pathways leading to persistence have been identified. H...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094483/ https://www.ncbi.nlm.nih.gov/pubmed/30108166 http://dx.doi.org/10.1128/mBio.00744-18 |
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author | Wilmaerts, Dorien Bayoumi, Mariam Dewachter, Liselot Knapen, Wouter Mika, Jacek T. Hofkens, Johan Dedecker, Peter Maglia, Giovanni Verstraeten, Natalie Michiels, Jan |
author_facet | Wilmaerts, Dorien Bayoumi, Mariam Dewachter, Liselot Knapen, Wouter Mika, Jacek T. Hofkens, Johan Dedecker, Peter Maglia, Giovanni Verstraeten, Natalie Michiels, Jan |
author_sort | Wilmaerts, Dorien |
collection | PubMed |
description | Bacterial populations harbor a small fraction of cells that display transient multidrug tolerance. These so-called persister cells are extremely difficult to eradicate and contribute to the recalcitrance of chronic infections. Several signaling pathways leading to persistence have been identified. However, it is poorly understood how the effectors of these pathways function at the molecular level. In a previous study, we reported that the conserved GTPase Obg induces persistence in Escherichia coli via transcriptional upregulation of the toxin HokB. In the present study, we demonstrate that HokB inserts in the cytoplasmic membrane where it forms pores. The pore-forming capacity of the HokB peptide is demonstrated by in vitro conductance measurements on synthetic and natural lipid bilayers, revealing an asymmetrical conductance profile. Pore formation is directly linked to persistence and results in leakage of intracellular ATP. HokB-induced persistence is strongly impeded in the presence of a channel blocker, thereby providing a direct link between pore functioning and persistence. Furthermore, the activity of HokB pores is sensitive to the membrane potential. This sensitivity presumably results from the formation of either intermediate or mature pore types depending on the membrane potential. Taken together, these results provide a detailed view on the mechanistic basis of persister formation through the effector HokB. |
format | Online Article Text |
id | pubmed-6094483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60944832018-08-24 The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage Wilmaerts, Dorien Bayoumi, Mariam Dewachter, Liselot Knapen, Wouter Mika, Jacek T. Hofkens, Johan Dedecker, Peter Maglia, Giovanni Verstraeten, Natalie Michiels, Jan mBio Research Article Bacterial populations harbor a small fraction of cells that display transient multidrug tolerance. These so-called persister cells are extremely difficult to eradicate and contribute to the recalcitrance of chronic infections. Several signaling pathways leading to persistence have been identified. However, it is poorly understood how the effectors of these pathways function at the molecular level. In a previous study, we reported that the conserved GTPase Obg induces persistence in Escherichia coli via transcriptional upregulation of the toxin HokB. In the present study, we demonstrate that HokB inserts in the cytoplasmic membrane where it forms pores. The pore-forming capacity of the HokB peptide is demonstrated by in vitro conductance measurements on synthetic and natural lipid bilayers, revealing an asymmetrical conductance profile. Pore formation is directly linked to persistence and results in leakage of intracellular ATP. HokB-induced persistence is strongly impeded in the presence of a channel blocker, thereby providing a direct link between pore functioning and persistence. Furthermore, the activity of HokB pores is sensitive to the membrane potential. This sensitivity presumably results from the formation of either intermediate or mature pore types depending on the membrane potential. Taken together, these results provide a detailed view on the mechanistic basis of persister formation through the effector HokB. American Society for Microbiology 2018-08-14 /pmc/articles/PMC6094483/ /pubmed/30108166 http://dx.doi.org/10.1128/mBio.00744-18 Text en Copyright © 2018 Wilmaerts et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Wilmaerts, Dorien Bayoumi, Mariam Dewachter, Liselot Knapen, Wouter Mika, Jacek T. Hofkens, Johan Dedecker, Peter Maglia, Giovanni Verstraeten, Natalie Michiels, Jan The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title | The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title_full | The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title_fullStr | The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title_full_unstemmed | The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title_short | The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage |
title_sort | persistence-inducing toxin hokb forms dynamic pores that cause atp leakage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094483/ https://www.ncbi.nlm.nih.gov/pubmed/30108166 http://dx.doi.org/10.1128/mBio.00744-18 |
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