Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA
Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA
复制标题
DOI：
10.1002/psc.835
复制
发表时间：
2007-04-01
影响因子：
2.1
通讯作者：
Zhuge Hong-Xiang
中科院分区：
文献类型：
--
作者：
Huang Xue-Wen;Pan Jie;Zhuge Hong-Xiang
本工作的目的是研究针对23S rRNA结构域II的反义肽核酸(PNA)对细菌翻译和生长的抑制作用。在本文中，我们报道了针对23S rRNA结构域II的PNA(G1138)或肽-PNA(G1138)在体外(在无细胞翻译系统中)和在体内都能抑制细菌的生长。抑菌浓度(IC50)为0.15，最小抑菌浓度(MIC)为10 pM。PNA(G1138)的体外抑菌效果略低于四环素(IC50=0.12µm)，但多肽PNA(G1138)对大肠埃希氏菌的MIC显著高于四环素(MIC=4µm)。基于相似集落形成单位(CFU)的进一步研究表明，10µm的多肽-PNA(G1138)具有杀菌作用，但杀菌效果不如四环素。然而，结果表明，多肽-PNA(G1138)处理具有剂量和序列依赖的杀菌作用，23S rRNA的G1138位是设计新型PNA类抗生素的可能序列靶点。版权所有(C)2007欧洲肽协会和John Wiley&Sons，Ltd.
The objective of this work was to study the inhibitory effects of antisense peptide nucleic acids (PNAs) targeted to domain II of 23S rRNA on bacterial translation and growth. In this paper, we report that PNA(G1138) or peptide-PNA(G1138) targeted to domain II of 23S rRNA can inhibit both translation in vitro (in a cell-free translation system) and bacterial growth in vivo. The inhibitory concentration (IC50) and the minimum inhibiting concentration (MIC) are 0.15 and 10 pm, respectively. The inhibition effect of PNA(G 1138) in vitro is somewhat lower than that of tetracycline (IC50 = 0.12 mu m), but the MIC of peptide-PNA(G1138) against Escherichica coli is significantly higher than that of tetracycline (MIC = 4 mu m). Further studies based on similar colony-forming unit (CFU) assays showed that peptide-PNA(G1138) at 10 mu m is bactericidal, but the bactericidal effect is less effective than that of tetracycline. Nevertheless, the results demonstrated that the peptide-PNA(G1138) treatment is bactericidal in a dose- and sequence-dependent manner and that the G1138 site of 23S rRNA is a possible sequence target for designing novel PNA-based antibiotics. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.