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...
Main Authors: | , |
---|---|
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 |