A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY npj Biofilms and Microbiomes Pub Date : 2024-11-14 DOI:10.1038/s41522-024-00603-8

Huanchang Chen, Haifeng Liu, Yanchun Gong, Rhys A Dunstan, Zhexiao Ma, Cui Zhou, Deyi Zhao, Miran Tang, Trevor Lithgow, Tieli Zhou

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Abstract

Bacteriophages (phages), viruses capable of infecting and lysing bacteria, are a promising alternative for treating infections from hypervirulent, antibiotic-resistant pathogens like Klebsiella pneumoniae, though narrow host range and phage resistance remain challenges. In this study, the hypervirulent K. pneumoniae NTUH-K2044 was used to purify phage ΦK2044, while two ΦK2044-resistant strains were used to purify two further phages: ΦKR1, and ΦKR8 from hospital sewage. A detailed characterization showed that ΦK2044 specifically killed KL1 capsule-type K. pneumoniae, while ΦKR1 and ΦKR8 targeted 13 different capsular serotypes. The phage cocktail (ΦK2044 + ΦKR1 + ΦKR8) effectively killed K. pneumoniae in biofilms, pre-treatment biofilm formation, and delayed phage-resistance. The phage cocktail improved 7-day survival in Galleria mellonella and mouse models and showed therapeutic potential in a catheter biofilm model. In summary, this proof-of-principle phage cocktail has a broad host range, including hypervirulent and highly drug-resistant K. pneumoniae, and serves as a promising starting point for optimizing phage therapy.

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一种克雷伯氏菌噬菌体鸡尾酒，可在体外和体内扩大宿主范围并延缓噬菌体的抗药性。

细菌噬菌体（噬菌体）是一种能够感染和裂解细菌的病毒，是治疗肺炎克雷伯氏菌等高病毒性、耐抗生素病原体感染的一种很有前景的替代方法，但宿主范围狭窄和噬菌体耐药性仍然是一个挑战。在这项研究中，我们利用肺炎克雷伯氏菌 NTUH-K2044 来纯化ΦK2044噬菌体，并利用两株ΦK2044耐药菌株来纯化另外两种噬菌体：KR1和ΦKR8。详细的特性分析表明，ΦK2044 专门杀灭 KL1 胶囊型肺炎双球菌，而 ΦKR1 和 ΦKR8 则针对 13 种不同的胶囊血清型。鸡尾酒噬菌体（ΦK2044 + ΦKR1 + ΦKR8）能有效杀死生物膜中的肺炎克菌，预处理生物膜的形成，并延缓噬菌体的抗药性。鸡尾酒噬菌体提高了小鼠和大鼠模型的 7 天存活率，并在导管生物膜模型中显示出治疗潜力。总之，这种经过原理验证的鸡尾酒噬菌体具有广泛的宿主范围，包括高病毒性和高耐药性肺炎双球菌，是优化噬菌体疗法的一个很有前景的起点。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.