Kiga Kotaro
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases.
Yakugaku Zasshi. 2025;145(8):679-688. doi: 10.1248/yakushi.24-00190-4.
The escalating crisis of antimicrobial resistance poses a grave threat to global health and medicine in the 21st century. Phage therapy has emerged as a promising alternative to conventional antibiotics in addressing this urgent issue. Phages, unlike traditional antibiotics, leave the healthy microbiome largely undisturbed by selectively targeting and infecting their bacterial host. Additionally, phages can be readily genetically engineered to enhance their efficacy against specific bacterial strains. While some countries are slowly developing new regulations and implementing phage therapy in the clinic, widespread societal adoption remains limited. Phage therapy has the potential to revolutionize infection treatment; however, the unique biological properties of phages necessitate a multifaceted approach for the societal implementation of phage therapy. Recent research has focused on genetically engineering phages to enhance their capabilities or confer novel functions. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have facilitated the development of phages that target specific genes. Furthermore, the emergence of tRNA-carrying phages and phages that inhibit bacterial defense systems represents new classes of genetically engineered phages with enhanced bactericidal properties.
21世纪,不断升级的抗生素耐药性危机对全球健康和医学构成了严重威胁。在解决这一紧迫问题方面,噬菌体疗法已成为传统抗生素的一种有前景的替代方法。与传统抗生素不同,噬菌体通过选择性地靶向和感染其细菌宿主,很大程度上不会干扰健康的微生物群。此外,噬菌体可以很容易地进行基因改造,以提高其对特定细菌菌株的疗效。虽然一些国家正在缓慢制定新法规并在临床中实施噬菌体疗法,但社会的广泛采用仍然有限。噬菌体疗法有可能彻底改变感染治疗方式;然而,噬菌体独特的生物学特性需要采取多方面的方法来实现噬菌体疗法的社会应用。最近的研究集中在对噬菌体进行基因改造,以增强其能力或赋予其新功能。成簇规律间隔短回文重复序列(CRISPR)-Cas系统促进了靶向特定基因的噬菌体的开发。此外,携带tRNA的噬菌体和抑制细菌防御系统的噬菌体的出现代表了具有增强杀菌特性的新型基因工程噬菌体。