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Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems

Toxin–antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the t...

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Detalles Bibliográficos
Autores principales: Deter, Heather S., Jensen, Roderick V., Mather, William H., Butzin, Nicholas C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535158/
https://www.ncbi.nlm.nih.gov/pubmed/28677629
http://dx.doi.org/10.3390/toxins9070211
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author Deter, Heather S.
Jensen, Roderick V.
Mather, William H.
Butzin, Nicholas C.
author_facet Deter, Heather S.
Jensen, Roderick V.
Mather, William H.
Butzin, Nicholas C.
author_sort Deter, Heather S.
collection PubMed
description Toxin–antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the toxin is neutralized when they form a complex. The ratio of antitoxin to toxin is significantly greater than 1.0 in the susceptible population (non-persister state), but this ratio is expected to become smaller during persistence. Analysis of multiple datasets (RNA-seq, ribosome profiling) and results from translation initiation rate calculators reveal multiple mechanisms that ensure a high antitoxin-to-toxin ratio in the non-persister state. The regulation mechanisms include both translational and transcriptional regulation. We classified E. coli type II TA systems into four distinct classes based on the mechanism of differential protein production between toxin and antitoxin. We find that the most common regulation mechanism is translational regulation. This classification scheme further refines our understanding of one of the fundamental mechanisms underlying bacterial persistence, especially regarding maintenance of the antitoxin-to-toxin ratio.
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spelling pubmed-55351582017-08-04 Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems Deter, Heather S. Jensen, Roderick V. Mather, William H. Butzin, Nicholas C. Toxins (Basel) Article Toxin–antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the toxin is neutralized when they form a complex. The ratio of antitoxin to toxin is significantly greater than 1.0 in the susceptible population (non-persister state), but this ratio is expected to become smaller during persistence. Analysis of multiple datasets (RNA-seq, ribosome profiling) and results from translation initiation rate calculators reveal multiple mechanisms that ensure a high antitoxin-to-toxin ratio in the non-persister state. The regulation mechanisms include both translational and transcriptional regulation. We classified E. coli type II TA systems into four distinct classes based on the mechanism of differential protein production between toxin and antitoxin. We find that the most common regulation mechanism is translational regulation. This classification scheme further refines our understanding of one of the fundamental mechanisms underlying bacterial persistence, especially regarding maintenance of the antitoxin-to-toxin ratio. MDPI 2017-07-04 /pmc/articles/PMC5535158/ /pubmed/28677629 http://dx.doi.org/10.3390/toxins9070211 Text en © 2017 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 Article
Deter, Heather S.
Jensen, Roderick V.
Mather, William H.
Butzin, Nicholas C.
Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title_full Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title_fullStr Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title_full_unstemmed Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title_short Mechanisms for Differential Protein Production in Toxin–Antitoxin Systems
title_sort mechanisms for differential protein production in toxin–antitoxin systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535158/
https://www.ncbi.nlm.nih.gov/pubmed/28677629
http://dx.doi.org/10.3390/toxins9070211
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