Wang Qian, Chen Ran, Liu Hui, Liu Yue, Li Jinmei, Wang Yueling, Jin Yan, Bai Yuanyuan, Song Zhen, Lu Xinglun, Wang Changyin, Hao Yingying
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Clinical Laboratory, Maternal and Child Health Care Hospital of Zaozhuang, Zaozhuang, Shandong, 277100, China.
Virus Res. 2024 Dec;350:199473. doi: 10.1016/j.virusres.2024.199473. Epub 2024 Oct 1.
The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G + C content of 51 %. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.
耐碳青霉烯类肺炎克雷伯菌（CRKP）对全球健康构成的威胁，因有效治疗方法有限而加剧。噬菌体是传统抗菌药物的有前景的替代物。然而，当前的噬菌体数据库有限。因此，鉴定和表征新的噬菌体可为治疗多重耐药细菌感染提供生物学选择。在此，我们报告了从医院污水中分离出的一种新型裂解性噬菌体vB_KpnP_23的表征。该噬菌体对产碳青霉烯酶的CRKP菌株表现出强大活性，其特征为具有二十面体头部、可收缩尾部，基因组由40,987个碱基对组成，G + C含量为51%。它能够靶向并裂解九种不同荚膜类型（K型）的CRKP，包括临床相关的ST11-K64，在各种环境条件下均表现出高溶菌效率和稳定性。至关重要的是，vB_KpnP_23缺乏毒力因子、抗菌抗性基因或tRNA，符合治疗应用的关键标准。噬菌体与抗生素联合使用的体外评估显示，vB_KpnP_23与美罗培南、左氧氟沙星或阿米卡星之间存在显著的协同效应。这种协同作用可使最低抑菌浓度（MIC）降低8倍，表明将这种噬菌体与上述抗生素联合使用的综合治疗可能会大幅提高药物疗效。这种方法不仅扩展了这些抗生素的临床应用，还在对抗抗生素耐药性方面取得了战略进展。具体而言，它强调了噬菌体-抗生素联合使用作为治疗CRKP引起的感染的有力工具的潜力，为缓解抗生素耐药病原体带来的公共卫生挑战提供了一条有前景的途径。
