Xing Jiabao, Han Rongjia, Zhao Jinxin, Zhang Yuying, Zhang Meng, Zhang Yichao, Zhang Hang, Nang Sue C, Zhai Yajun, Yuan Li, Wang Shanmei, Wu Hua
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.
Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Microbiol Res. 2025 Apr;293:128083. doi: 10.1016/j.micres.2025.128083. Epub 2025 Jan 31.
Multi-drug resistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae strains are spreading globally at an alarming rate, emerging as one of the most serious threats to global public health. The formidable challenges posed by the current arsenal of antimicrobials highlight the urgent need for novel strategies to combat K. pneumoniae infections. This review begins with a comprehensive analysis of the global dissemination of virulence factors and critical resistance profiles in K. pneumoniae, followed by an evaluation of the accessibility of novel therapeutic approaches for treating K. pneumoniae in clinical settings. Among these, phage therapy stands out for its considerable potential in addressing life-threatening K. pneumoniae infections. We critically examine the existing preclinical and clinical evidence supporting phage therapy, identifying key limitations that impede its broader clinical adoption. Additionally, we rigorously explore the role of genetic engineering in expanding the host range of K. pneumoniae phages, and discuss the future trajectory of this technology. In light of the 'Bad Bugs, No Drugs' era, we advocate leveraging artificial intelligence and deep learning to optimize and expand the application of phage therapy, representing a crucial advancement in the fight against the escalating threat of K. pneumoniae infections.
多重耐药和耐碳青霉烯类的高毒力肺炎克雷伯菌菌株正在全球以惊人的速度传播，成为对全球公共卫生最严重的威胁之一。当前抗菌药物 arsenal 所带来的巨大挑战凸显了对抗肺炎克雷伯菌感染的新策略的迫切需求。本综述首先全面分析了肺炎克雷伯菌中毒力因子的全球传播和关键耐药谱，随后评估了临床环境中治疗肺炎克雷伯菌的新型治疗方法的可及性。其中，噬菌体疗法因其在解决危及生命的肺炎克雷伯菌感染方面的巨大潜力而脱颖而出。我们批判性地审视了支持噬菌体疗法的现有临床前和临床证据，确定了阻碍其更广泛临床应用的关键限制。此外，我们严格探索基因工程在扩大肺炎克雷伯菌噬菌体宿主范围方面的作用，并讨论该技术的未来发展轨迹。鉴于“超级细菌，无药可治”的时代，我们主张利用人工智能和深度学习来优化和扩大噬菌体疗法的应用，这是对抗肺炎克雷伯菌感染不断升级威胁的关键进展。
