中科院南海海洋研究所研究员王晓雪等近日在Nature Chemical Biology（《自然化学生物学》）发表论文——A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS，该成果由中国科学院南海海洋所、美国宾州州立大学和布朗大学共同完成。
南海海洋所等揭示毒素-抗毒素系统全新调控机制
王晓雪等研究发现的这种新型的毒素YjdO(又称GhoT)－抗毒素YjdK (又称GhoS)系统，是目前所知的第一个V型毒素-抗毒素系统（toxin-antitoxin system），GhoT是一种细胞膜裂解肽（membrane lytic peptide），可引起“GhoS”细胞（质膜破裂剩下保持原来形态和大小的裂解细胞）。体外RNA降解实验、定量RT-PCR和全转录组研究，查明GhoS通过特异切割GhoT mRNA抑制了GhoT的毒性，揭示了毒素-抗毒素系统全新的调控机制。
据介绍，毒素-抗毒素系统实际广泛存在于细菌等原核生物中，通常是由两个共表达的基因组成，其中一个为基因编码不稳定的抗毒素蛋白（antitoxin），另一个为基因编码稳定的毒素蛋白（toxin）。两个蛋白相互作用形成毒素-抗毒素复合物，从而抑制毒素蛋白对细菌的致死作用。当处于营养缺乏等不良生长条件下时，由于蛋白酶的降解作用，不稳定的抗毒素蛋白减少，产生游离的毒素蛋白，导致细菌生长抑制和死亡。
该研究有助于更深入地了解水平基因转移在生物进化的作用，为开辟现代抗菌药物治疗的新途径具有重要意义。
该成果得到了国家重大基础研究项目（973计划）和国家自然科学基金等项目资助。(生物谷Bioon.com)
doi:10.1038/nchembio.1062
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A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS.
Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, Quiroga C, Zheng K, Herrmann T, Peti W, Benedik MJ, Page R, Wood TK.
Among bacterial toxin-antitoxin systems, to date no antitoxin has been identified that functions by cleaving toxin mRNA. Here we show that YjdO (renamed GhoT) is a membrane lytic peptide that causes ghost cell formation (lysed cells with damaged membranes) and increases persistence (persister cells are tolerant to antibiotics without undergoing genetic change). GhoT is part of a new toxin-antitoxin system with YjdK (renamed GhoS) because in vitro RNA degradation studies, quantitative real-time reverse-transcription PCR and whole-transcriptome studies revealed that GhoS masks GhoT toxicity by cleaving specifically yjdO (ghoT) mRNA. Alanine substitutions showed that Arg28 is important for GhoS activity, and RNA sequencing indicated that the GhoS cleavage site is rich in U and A. The NMR structure of GhoS indicates it is related to the CRISPR-associated-2 RNase, and GhoS is a monomer. Hence, GhoT-GhoS is to our knowledge the first type V toxin-antitoxin system where a protein antitoxin inhibits the toxin by cleaving specifically its mRNA.
