反义技术在新型抗菌药物研发中的应用

Applications of antisense technology in discovery and development of novel antibacterial drugs

抗生素耐药菌株的出现及迅速蔓延对人类生命安全构成了严重威胁,为解决这一问题,迫切需要研发新型抗菌药物。反义技术在这一领域中发挥着越来越重要的作用。本文重点综述了反义技术在以下几个方面的应用,包括寻找新的抗菌药物作用靶点、利用反义技术构建敏感菌从天然化合物库中筛选新型抗菌药物、采用反义技术抑制耐药基因的表达从而逆转耐药菌对现有抗生素的敏感性。另外,本文还讨论了人工合成的反义核酸的抗菌活性,并分析了其作为抗菌药物存在的问题及今后的发展前景。

Antibiotic-resistance has become a serious problem to human health.Innovative approaches are urgently required for both antimicrobial drug discovery and reversal of resistance.Great success has been achieved since the introduction of antisense technology.This review focuses on the applications of antisense technology in the aspects including identification and validation of novel antibacterial drug targets,screening of antibacterial drugs from natural products using hypersensitized strains engineered by inducible antisense RNA,and inhibition of antibiotic-resistance genes to reverse susceptibility of antibiotic-resistant strains to currently used antibiotics.In addition,the antibacterial activities,the shortcomings and prospects as antibacterial drugs of synthetic antisense oligodeoxynucleotides and their analogs are also assessed in this review.