Zhou Fang, Wang Kexiao, Ji Shuai, Liao Xiaochen, Zhang Wenwen, Teng Tieshan, Wang Li, Li Qiming
Henan Province Engineering Technology Research Center of Rapid-Accuracy Medical Diagnostics, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, China.
The Joint National Laboratory of Antibody Drug Engineering, Henan University, Kaifeng, China.
Microbiol Spectr. 2025 Jul;13(7):e0163324. doi: 10.1128/spectrum.01633-24. Epub 2025 May 16.
As the overuse of antibiotics has not yet been strictly limited in urban areas, drug-resistant has become a fatal pressure for bacteremia treatment. Considering the outstanding performance of bacteriophages , bacteriophages may serve as an alternative to heal chronic refractory infections. In this study, a 49,890 bp double-stranded circular DNA phage, Henu8, was isolated and was able to lyse the group of strains tested in this study. Prominent biological characterization revealed that the highly adsorbed bacteriophage Henu8 could form a fully transparent plaque with a narrow translucent halo. The optimal multiplicity of infection of the bacteriophage Henu8 was 0.01, with a burst size of 275 PFU/cell. Genomic analysis revealed a G + C content of 44.17% Henu8, in which 65 open reading frames were located, which could be assigned as a new species in the genus of the subfamily . The effective antibacterial ability and the obvious biofilm destruction and inhibition capability of phage Henu8 were observed. The time-killing assay demonstrated the synergetic potential of Henu8 with antibiotics for eradication. Henu8 has profound medicinal potential in a mouse bacteremia model. These studies indicate that Henu8 is a novel bacteriophage with therapeutic potential alone or in combination with antibiotics for clinical treatment.IMPORTANCEThe findings described in this study constitute concrete evidence that it is possible to significantly synergize the antimicrobial activity of bacteriophages and antibiotics. We showed that the newly isolated potent bacteriophage Henu8 lyses rapidly but tends to produce resistant bacteria. The bacteriophage Henu8 has synergistic antimicrobial effects with several antibiotics and is not susceptible to developing resistance. These results provide further evidence that bacterial resistance to phages arises, possibly at an adaptive cost to sensitivity to antibiotics. Therefore, the findings of this study are important for increasing the potential of phages for clinical applications and developing new approaches to improve their therapeutic efficacy against bacterial drug resistance.
由于抗生素的过度使用在城市地区尚未得到严格限制，耐药性已成为治疗菌血症的致命压力。鉴于噬菌体的出色表现，噬菌体可能成为治疗慢性难治性感染的替代方法。在本研究中，分离出了一个49,890 bp的双链环状DNA噬菌体Henu8，它能够裂解本研究中测试的菌株组。显著的生物学特性表明，高度吸附的噬菌体Henu8能够形成一个完全透明的噬菌斑，并带有狭窄的半透明晕圈。噬菌体Henu8的最佳感染复数为0.01，裂解量为275 PFU/细胞。基因组分析显示Henu8的G + C含量为44.17%，其中有65个开放阅读框，可被归类为亚科属中的一个新物种。观察到噬菌体Henu8具有有效的抗菌能力以及明显的生物膜破坏和抑制能力。时间杀菌试验证明了Henu8与抗生素联合根除的协同潜力。在小鼠菌血症模型中，Henu8具有深远的药用潜力。这些研究表明，Henu8是一种新型噬菌体，单独使用或与抗生素联合使用具有临床治疗潜力。重要性本研究中描述的发现构成了具体证据，表明噬菌体和抗生素的抗菌活性有可能显著协同。我们表明，新分离的强效噬菌体Henu8能迅速裂解，但倾向于产生耐药菌。噬菌体Henu8与几种抗生素具有协同抗菌作用，且不易产生耐药性。这些结果进一步证明，细菌对噬菌体产生抗性，可能是以对抗生素敏感性的适应性代价为代价的。因此，本研究的发现对于提高噬菌体在临床应用中的潜力以及开发新方法以提高其对细菌耐药性的治疗效果具有重要意义。
