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合成 DNA / RNA 类似物显示强大的抗菌活性

By LabMedica International staff writers
Posted on 19 Nov 2013

图片：鲍氏不动杆菌的扫描电子显微镜图像，显示其基因组（外圈）和异型岛序列（内圈，红色）（照片由美国疾病控制中心的 J. Carr、以及耶鲁大学的T. Gianoulis 和 D. Massa 提供）

图片：鲍氏不动杆菌的扫描电子显微镜图像，显示其基因组（外圈）和异型岛序列（内圈，红色）（照片由美国疾病控制中心的 J. Carr、以及耶鲁大学的T. Gianoulis 和 D. Massa 提供）

肽共轭的磷酰二胺吗啉代寡核苷酸 (PPMO) 是合成的 DNR/RNA 类似物，是特定基因的静默表达，研究发现 PPMO 体外和体内均能抑制不动杆菌的生长。

俄勒冈州立大（美国俄勒冈州科瓦利斯）的研究人员试图确定 PPMO 体外和体内时是否以鲁氏不动杆菌和鲍氏不动杆菌的必需基因为靶点。他们使用药物最低抑菌浓度 (MIC) 和免疫活性评估了 PPMO 的体外培养物，并使用鼻内 PPMO 治疗的小鼠肺感染模型进行了体内评估。

研究结果已发表于 2013 年 10 月 14 日的网络版《传染病期刊》(Journal of Infectious Diseases)，揭示最有效的 PPMO 检测项目为 (RXR) 4-AcpP，后者以 acpP 基因为靶点。PPMO 降低鲁氏不动杆菌和鲍氏不动杆菌的免疫活性，每毫升形成 1000 多个菌落单位，MIC 为 5-8 倍。(RXR)4-AcpP 治疗的小鼠存活时间更长，比乱序对照 PPMO 或磷酸盐缓冲盐治疗的小鼠炎症少，且细菌肺负担小。治疗可以延迟至感染后，而仍能增高存活率。

“PPMO 杀死细菌的作用机理引起了巨大的变革，”第一作者，俄勒冈州立大的微生物学教授 Bruce Geller 说。“他们几乎可以被合成以任何基因为靶点的序列，并以此避免产生抗生素耐药性，并避免产生广谱抗生素相关的负面影响。”

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