Schuster Christopher F, Bertram Ralph
Section of Microbiology & MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, University of Tübingen, 72076 Tübingen, Germany.
Toxins (Basel). 2016 May 5;8(5):140. doi: 10.3390/toxins8050140.
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.
毒素-抗毒素（TA）系统是在大多数原核生物中发现的小遗传元件。它们编码干扰重要细胞功能的毒素蛋白，并被抗毒素所抵消。根据抗毒素的化学性质（蛋白质或RNA）以及它们如何控制毒素的活性，TA系统目前分为六种不同类型。在金黄色葡萄球菌中已鉴定出构成TA I型、II型和III型的基因。mazEF位点的毒素MazF是一种序列特异性核糖核酸酶，可切割许多转录本，包括那些编码致病因子的转录本。两个yefM-yoeB旁系同源物代表两个独立但自我调节的TA系统，可产生核糖体依赖性核糖核酸酶。此外，omega/epsilon/zeta构成一个三方TA系统，据推测在抗性因子的稳定中起作用。SprA1/SprA1AS和SprF1/SprG1系统由RNA抗毒素进行转录后调控，并编码小的膜损伤蛋白。通过毒素蛋白和抗毒素RNA之间的相互作用控制的TA系统已在金黄色葡萄球菌的计算机模拟中鉴定出来，但尚未得到实验证实。对TA系统与金黄色葡萄球菌病理生理学之间可能联系的更深入研究将揭示，这些基因位点是否可能代表可成药靶点。将葡萄球菌TA毒素修饰为环肽抗生素突出了TA系统作为尚未充分开发的药物发现来源的潜力。
