Abstract
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.
Highlights
Staphylococcus aureus is a ubiquitous Gram positive commensal, colonizing about one third of the world’s human population
Bacterial toxins are considered to be poisonous compounds associated with pathogens targeting other bacteria or host cells
Research on type I TA systems in S. aureus was strongly promoted by investigations of the enterococcal plasmid pAD1 [37,38], and by the identification of numerous small non-coding RNAs [39,40,41,42]
Summary
Staphylococcus aureus is a ubiquitous Gram positive commensal, colonizing about one third of the world’s human population. The term “bacterial toxin” extends beyond factors that primarily harm other organisms, and includes proteins which interfere with vital cellular functions of the prokaryotic cell from which they are encoded. By default, such toxins are negatively controlled by other proteins or RNAs to form so called toxin-antitoxin (TA) systems [5,6,7]. TA systems have so far been characterized in the non-pathogenic S. equorum [35,36] and in S. aureus For the latter, we here provide an overview on both experimentally verified and in silico predicted systems, all of which belong to TA types I, II and III
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