Zhu Rui, Wang Ruilin, Fei Bing, Lu Ruici, You Xiaojuan, Liu Xinwei, Wang Chunxia, Li Yongwei
Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, China.
The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China.
Front Cell Infect Microbiol. 2025 Sep 4;15:1610625. doi: 10.3389/fcimb.2025.1610625. eCollection 2025.
Carbapenem-resistant (CRKP) has emerged as a critical global public health threat, characterized by high infection rates, elevated mortality, and limited therapeutic options. In this study, we isolated and characterized a novel bacteriophage (phage), designated as HZJ31, which exhibited potent lytic activity against CRKP strains. Phylogenetic and genomic analyses revealed that phage HZJ31 belongs to the order and lacks virulence factors, antibiotic resistance genes, and lysogeny-related elements, supporting its suitability for therapeutic applications. Phage HZJ31 exhibits remarkable anti-biofilm activity by preventing biofilm formation and disrupting established biofilms, with bacterial reduction rates exceeding 70% (<0.05). In combination with Tigecycline, it significantly enhanced bactericidal efficacy, delayed the emergence of phage resistant mutants, and improved survival rates in larvae infection models. Compared to the bacterial-infected group, which had 80% larval mortality at 96 h, treatment with HZJ31 or TGC alone led to 50% and 60% survival, while their combination improved survival to 70% ( < 0.05). Notably, the phage-resistant mutant, which emerged due to capsule loss, resulted in reduced growth and virulence, while regaining sensitivity to certain antibiotics (such as gentamicin), indicating a fitness cost associated with phage resistance. Collectively, these findings provide valuable insights into phage-antibiotic synergy and underscore the promising clinical potential of phage HZJ31 as a therapeutic agent against CRKP infections.
耐碳青霉烯类肺炎克雷伯菌（CRKP）已成为全球重大公共卫生威胁，其特点是感染率高、死亡率高且治疗选择有限。在本研究中，我们分离并鉴定了一种新型噬菌体（phage），命名为HZJ31，它对CRKP菌株表现出强大的裂解活性。系统发育和基因组分析表明，噬菌体HZJ31属于该目，且缺乏毒力因子、抗生素抗性基因和溶原性相关元件，这支持了其在治疗应用中的适用性。噬菌体HZJ31通过防止生物膜形成和破坏已形成的生物膜表现出显著的抗生物膜活性，细菌减少率超过70%（<0.05）。与替加环素联合使用时，它显著增强了杀菌效果，延迟了噬菌体抗性突变体的出现，并提高了幼虫感染模型中的存活率。与细菌感染组相比，该组在96小时时幼虫死亡率为80%，单独使用HZJ31或TGC治疗导致存活率分别为50%和60%，而它们的联合使用将存活率提高到70%（<0.05）。值得注意的是，由于荚膜丢失而出现的噬菌体抗性突变体导致生长和毒力降低，同时恢复了对某些抗生素（如庆大霉素）的敏感性，表明与噬菌体抗性相关的适应性代价。总的来说，这些发现为噬菌体 - 抗生素协同作用提供了有价值的见解，并强调了噬菌体HZJ31作为治疗CRKP感染的治疗剂的潜在临床应用前景。
