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Background <p><i>Pseudomonas aeruginosa</i> poses significant therapeutic challenges due to its acquired and innate resistance mechanisms. Bacteriophages and their purified lysis proteins have emerged as promising alternatives for combating <i>P. aeruginosa</i> infections.</p> Methods <p>Phage P7869 was isolated from hospital sewage and characterized. Whole-genome sequencing was conducted to elucidate the genomic features of P7869. The recombinant endolysin Lys7869 was expressed and purified using a prokaryotic system, and its stability, minimum inhibitory concentration and antimicrobial spectrum were assessed.</p> Results <p>P7869 exhibited a narrow host range and high stability. Genomic analysis confirmed its temperate lifestyle, yet its recombinant endolysin, Lys7869, demonstrated therapeutic potential. Lys7869 demonstrated high stability across a broad range (pH 4–7, 4–50&#xa0;°C), making it suitable for diverse formulation and storage conditions. It exhibited potent activity with a minimum inhibitory concentration of 500 ng/mL. Lys7869 displayed a broader antimicrobial spectrum against chloroform-permeabilized Gram-negative pathogens, suggesting its potential as a versatile agent to combat various multidrug-resistant strains.</p> Conclusions <p>This study identified a novel temperate phage, P7869, and highlights its endolysin Lys7869 as a highly promising antibacterial agent. These findings lay a critical foundation for protein engineering efforts to enhance its outer-membrane penetration and create next-generation enzybiotics against multidrug-resistant <i>Pseudomonas aeruginosa</i> infections.</p>

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A temperate phage encoding a catalytically active endolysin: characterization of phage P7869 and its Lys7869 against Pseudomonas aeruginosa

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月11日

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  • Jiao Feng,
  • Xuexue Wang,
  • Liangyu Wang,
  • Yuming Zhang,
  • Xiaogang Cui,
  • Yan Meng,
  • Xiaoxia Zhou,
  • Changxin Wu,
  • Chenrui Hou

摘要

Background

Pseudomonas aeruginosa poses significant therapeutic challenges due to its acquired and innate resistance mechanisms. Bacteriophages and their purified lysis proteins have emerged as promising alternatives for combating P. aeruginosa infections.

Methods

Phage P7869 was isolated from hospital sewage and characterized. Whole-genome sequencing was conducted to elucidate the genomic features of P7869. The recombinant endolysin Lys7869 was expressed and purified using a prokaryotic system, and its stability, minimum inhibitory concentration and antimicrobial spectrum were assessed.

Results

P7869 exhibited a narrow host range and high stability. Genomic analysis confirmed its temperate lifestyle, yet its recombinant endolysin, Lys7869, demonstrated therapeutic potential. Lys7869 demonstrated high stability across a broad range (pH 4–7, 4–50 °C), making it suitable for diverse formulation and storage conditions. It exhibited potent activity with a minimum inhibitory concentration of 500 ng/mL. Lys7869 displayed a broader antimicrobial spectrum against chloroform-permeabilized Gram-negative pathogens, suggesting its potential as a versatile agent to combat various multidrug-resistant strains.

Conclusions

This study identified a novel temperate phage, P7869, and highlights its endolysin Lys7869 as a highly promising antibacterial agent. These findings lay a critical foundation for protein engineering efforts to enhance its outer-membrane penetration and create next-generation enzybiotics against multidrug-resistant Pseudomonas aeruginosa infections.