Li Juan, Feng Yu, Luo Huan, Fang Qingqing, Yang Yongqiang, Zong Zhiyong
Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China.
Front Microbiol. 2024 Sep 23;15:1462459. doi: 10.3389/fmicb.2024.1462459. eCollection 2024.
Lytic bacteriophages (phages) are promising clinically viable therapeutic options against carbapenem-resistant (CRKP). In China, the predominant strains are those assigned to sequence type 11 and capsular type 64 (ST11-KL64). The emergence of phage resistance is a major bottleneck hindering effective phage therapy, requiring more new phages to provide the flexibility for creating different phage cocktails. However, the majority of phages against ST11-KL64 CRKP belong to the genus of the family , which limits the options for constructing cocktails. We recovered a novel lytic phage of the genus within the family against ST11-KL64 CRKP from a river in China. We phenotypically characterized this phage and obtained its genome sequence for analysis. This phage can inhibit the growth of ST11-KL64 CRKP for 6.5 h at a 0.1 multiplicity of infection and exhibits a narrow host range, being unable to attack CRKP strains of the other 30 capsular types. This phage carries no genes encoding antimicrobial resistance, virulence, or lysogeny. It is stable across a wide range of temperatures and pH values, making it suitable for phage therapy. Unlike other phages, P01 has two tail spike proteins and a unique tail fiber protein. The distinct tail composition of this phage contributes to its activity against ST11-KL64 CRKP and its narrow host range. Taken together, we recovered a phage of a novel viral species with the potential for therapy, which expands the phage biobank against CRKP.
裂解性噬菌体有望成为临床上对抗耐碳青霉烯类肺炎克雷伯菌(CRKP)的可行治疗选择。在中国,主要菌株是那些属于序列型11和荚膜型64(ST11-KL64)的菌株。噬菌体抗性的出现是阻碍有效噬菌体治疗的主要瓶颈,需要更多新的噬菌体来为创建不同的噬菌体鸡尾酒提供灵活性。然而,大多数针对ST11-KL64 CRKP的噬菌体属于[此处原文缺失噬菌体所属的科名]科的[此处原文缺失噬菌体所属的属名]属,这限制了构建鸡尾酒的选择。我们从中国的一条河流中分离出一种针对ST11-KL64 CRKP的新型[此处原文缺失噬菌体所属的科名]科[此处原文缺失噬菌体所属的属名]属裂解性噬菌体。我们对该噬菌体进行了表型特征分析,并获得了其基因组序列进行分析。这种噬菌体在感染复数为0.1时可抑制ST11-KL64 CRKP的生长6.5小时,并且宿主范围狭窄,无法攻击其他30种荚膜型的CRKP菌株。该噬菌体不携带编码抗菌抗性、毒力或溶原性的基因。它在广泛的温度和pH值范围内都很稳定,适合用于噬菌体治疗。与其他[此处原文缺失噬菌体所属的属名]噬菌体不同,P01有两个尾刺蛋白和一个独特的尾丝蛋白。这种噬菌体独特的尾部组成有助于其对ST11-KL64 CRKP的活性及其狭窄的宿主范围。综上所述,我们分离出一种具有治疗潜力的新型病毒物种的噬菌体,这扩展了针对CRKP的噬菌体生物库。