Toxin-Antitoxin Systems of Staphylococcus aureus

Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activ...

Full description

Bibliographic Details
Main Authors: Christopher F. Schuster, Ralph Bertram
Format: Article
Language:English
Published: MDPI AG 2016-05-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/8/5/140
_version_ 1828354583638835200
author Christopher F. Schuster
Ralph Bertram
author_facet Christopher F. Schuster
Ralph Bertram
author_sort Christopher F. Schuster
collection DOAJ
description Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery.
first_indexed 2024-04-14T02:27:01Z
format Article
id doaj.art-d80549b91dc6400ab9fd2da36cd5507e
institution Directory Open Access Journal
issn 2072-6651
language English
last_indexed 2024-04-14T02:27:01Z
publishDate 2016-05-01
publisher MDPI AG
record_format Article
series Toxins
spelling doaj.art-d80549b91dc6400ab9fd2da36cd5507e2022-12-22T02:17:50ZengMDPI AGToxins2072-66512016-05-018514010.3390/toxins8050140toxins8050140Toxin-Antitoxin Systems of Staphylococcus aureusChristopher F. Schuster0Ralph Bertram1Section of Microbiology & MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UKInterfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, University of Tübingen, 72076 Tübingen, GermanyToxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery.http://www.mdpi.com/2072-6651/8/5/140Staphylococcus aureustoxin-antitoxin systemplasmid addictionMazEFYefM-YoeBRNaseSprA1-SprA1ASSprFGTenpINOmega-Epsilon-Zeta
spellingShingle Christopher F. Schuster
Ralph Bertram
Toxin-Antitoxin Systems of Staphylococcus aureus
Toxins
Staphylococcus aureus
toxin-antitoxin system
plasmid addiction
MazEF
YefM-YoeB
RNase
SprA1-SprA1AS
SprFG
TenpIN
Omega-Epsilon-Zeta
title Toxin-Antitoxin Systems of Staphylococcus aureus
title_full Toxin-Antitoxin Systems of Staphylococcus aureus
title_fullStr Toxin-Antitoxin Systems of Staphylococcus aureus
title_full_unstemmed Toxin-Antitoxin Systems of Staphylococcus aureus
title_short Toxin-Antitoxin Systems of Staphylococcus aureus
title_sort toxin antitoxin systems of staphylococcus aureus
topic Staphylococcus aureus
toxin-antitoxin system
plasmid addiction
MazEF
YefM-YoeB
RNase
SprA1-SprA1AS
SprFG
TenpIN
Omega-Epsilon-Zeta
url http://www.mdpi.com/2072-6651/8/5/140
work_keys_str_mv AT christopherfschuster toxinantitoxinsystemsofstaphylococcusaureus
AT ralphbertram toxinantitoxinsystemsofstaphylococcusaureus