中科院南海海洋研究所研究員王曉雪等近日在Nature Chemical Biology（《自然化學(xué)生物學(xué)》）發(fā)表論文——A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS,，該成果由中國科學(xué)院南海海洋所、美國賓州州立大學(xué)和布朗大學(xué)共同完成,。
南海海洋所等揭示毒素-抗毒素系統(tǒng)全新調(diào)控機制
王曉雪等研究發(fā)現(xiàn)的這種新型的毒素YjdO(又稱GhoT)－抗毒素YjdK (又稱GhoS)系統(tǒng),，是目前所知的第一個V型毒素-抗毒素系統(tǒng)（toxin-antitoxin system），GhoT是一種細胞膜裂解肽（membrane lytic peptide）,，可引起“GhoS”細胞（質(zhì)膜破裂剩下保持原來形態(tài)和大小的裂解細胞）,。體外RNA降解實驗、定量RT-PCR和全轉(zhuǎn)錄組研究,，查明GhoS通過特異切割GhoT mRNA抑制了GhoT的毒性,，揭示了毒素-抗毒素系統(tǒng)全新的調(diào)控機制。
據(jù)介紹,，毒素-抗毒素系統(tǒng)實際廣泛存在于細菌等原核生物中,，通常是由兩個共表達的基因組成，其中一個為基因編碼不穩(wěn)定的抗毒素蛋白（antitoxin）,，另一個為基因編碼穩(wěn)定的毒素蛋白（toxin）,。兩個蛋白相互作用形成毒素-抗毒素復(fù)合物，從而抑制毒素蛋白對細菌的致死作用,。當處于營養(yǎng)缺乏等不良生長條件下時,，由于蛋白酶的降解作用，不穩(wěn)定的抗毒素蛋白減少,，產(chǎn)生游離的毒素蛋白,，導(dǎo)致細菌生長抑制和死亡。
該研究有助于更深入地了解水平基因轉(zhuǎn)移在生物進化的作用,，為開辟現(xiàn)代抗菌藥物治療的新途徑具有重要意義,。
該成果得到了國家重大基礎(chǔ)研究項目（973計劃）和國家自然科學(xué)基金等項目資助。(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.
