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Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions
Persistence is a phenomenon during which a small fraction of a total bacterial population survives treatment with high concentrations of antibiotics for an extended period of time. In conjunction with biofilms, antibiotic persisters represent a major cause of recalcitrant and recurring infections, r...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874710/ https://www.ncbi.nlm.nih.gov/pubmed/29389876 http://dx.doi.org/10.3390/ph11010014 |
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author | Cabral, Damien J. Wurster, Jenna I. Belenky, Peter |
author_facet | Cabral, Damien J. Wurster, Jenna I. Belenky, Peter |
author_sort | Cabral, Damien J. |
collection | PubMed |
description | Persistence is a phenomenon during which a small fraction of a total bacterial population survives treatment with high concentrations of antibiotics for an extended period of time. In conjunction with biofilms, antibiotic persisters represent a major cause of recalcitrant and recurring infections, resulting in significant morbidity and mortality. In this review, we discuss the clinical significance of persister cells and the central role of bacterial metabolism in their formation, specifically with respect to carbon catabolite repression, sugar metabolism, and growth regulation. Additionally, we will examine persister formation as an evolutionary strategy used to tolerate extended periods of stress and discuss some of the response mechanisms implicated in their formation. To date, the vast majority of the mechanistic research examining persistence has been conducted in artificial in vitro environments that are unlikely to be representative of host conditions. Throughout this review, we contextualize the existing body of literature by discussing how in vivo conditions may create ecological niches that facilitate the development of persistence. Lastly, we identify how the development of next-generation sequencing and other “big data” tools may enable researchers to examine persistence mechanisms within the host to expand our understanding of their clinical importance. |
format | Online Article Text |
id | pubmed-5874710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58747102018-04-02 Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions Cabral, Damien J. Wurster, Jenna I. Belenky, Peter Pharmaceuticals (Basel) Review Persistence is a phenomenon during which a small fraction of a total bacterial population survives treatment with high concentrations of antibiotics for an extended period of time. In conjunction with biofilms, antibiotic persisters represent a major cause of recalcitrant and recurring infections, resulting in significant morbidity and mortality. In this review, we discuss the clinical significance of persister cells and the central role of bacterial metabolism in their formation, specifically with respect to carbon catabolite repression, sugar metabolism, and growth regulation. Additionally, we will examine persister formation as an evolutionary strategy used to tolerate extended periods of stress and discuss some of the response mechanisms implicated in their formation. To date, the vast majority of the mechanistic research examining persistence has been conducted in artificial in vitro environments that are unlikely to be representative of host conditions. Throughout this review, we contextualize the existing body of literature by discussing how in vivo conditions may create ecological niches that facilitate the development of persistence. Lastly, we identify how the development of next-generation sequencing and other “big data” tools may enable researchers to examine persistence mechanisms within the host to expand our understanding of their clinical importance. MDPI 2018-02-01 /pmc/articles/PMC5874710/ /pubmed/29389876 http://dx.doi.org/10.3390/ph11010014 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Cabral, Damien J. Wurster, Jenna I. Belenky, Peter Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title | Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title_full | Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title_fullStr | Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title_full_unstemmed | Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title_short | Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions |
title_sort | antibiotic persistence as a metabolic adaptation: stress, metabolism, the host, and new directions |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874710/ https://www.ncbi.nlm.nih.gov/pubmed/29389876 http://dx.doi.org/10.3390/ph11010014 |
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