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Purpose <p>The global rise in multidrug-resistant (MDR) <i>Klebsiella pneumoniae</i>, a critical ESKAPE pathogen, has outpaced the development of effective antibiotics. Bacteriophage therapy offers a promising alternative, but therapeutic candidates must be carefully selected for broad activity, genetic safety, synergistic cocktail performance, and clinical stability.</p> Methods <p>We isolated and characterized six novel lytic phages (vB_Kpn_AM.K1 to vB_Kpn_AM.K6) targeting <i>K. pneumoniae</i> by assessing morphology, host range, growth kinetics, physicochemical stability, and resistance frequency. Genomes were sequenced to confirm absence of lysogeny and virulence genes. Infection dynamics was visualized via fluorescence microscopy. Phage activity was tested across 60 different MDR <i>K. pneumoniae</i> clinical isolates, obtained from diverse sources such as blood, sputum, occult feces, urine etc.</p> Results <p>All six isolated phages were identified as novel dsDNA phages belonging to <i>Caudoviricetes</i>, with genome sizes ranging from 111 to 169 Kbp, devoid of virulence and AMR genes and demonstrating strong bacteriolytic activity. Growth kinetics indicated burst sizes varying from 12-148 PFU/infected cell. The phages displayed stability between 4-50°C, pH 4 -10 and sustained complete activity after lyophilization. More significantly, the phages and their cocktail combinations could effectively kill 93% of MDR <i>K. pneumoniae</i> clinical isolates.</p> Conclusion <p>These findings establish a panel of genetically safe, phenotypically diverse phages with broad and synergistic activity against <i>MDR K. pneumoniae</i>. The unique replication phenotypes and formulation stability highlight their potential for therapeutic development and deployment in clinical or resource-limited settings.</p>

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Novel bacteriophages effectively target multidrug-resistant clinical isolates of Klebsiella pneumoniae

  • 期刊论文

  • 发表日期：

    2025年10月17日

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  • Malavika Binitha Hari,
  • A. L. Sreelekshmi,
  • Pradeesh Babu,
  • Abhijith Pulimoottil Jaykumar,
  • Sivaraj Barath,
  • Sharayu Magar,
  • Sutharsan Govindarajan,
  • John Bernet Johnson,
  • Anil Kumar,
  • Jayalekshmi Haripriyan,
  • Victor Nizet,
  • Jason Gill,
  • Lindsey Camara,
  • Dwayne R. Roach,
  • Bipin G. Nair,
  • Geetha B. Kumar

摘要

Purpose

The global rise in multidrug-resistant (MDR) Klebsiella pneumoniae, a critical ESKAPE pathogen, has outpaced the development of effective antibiotics. Bacteriophage therapy offers a promising alternative, but therapeutic candidates must be carefully selected for broad activity, genetic safety, synergistic cocktail performance, and clinical stability.

Methods

We isolated and characterized six novel lytic phages (vB_Kpn_AM.K1 to vB_Kpn_AM.K6) targeting K. pneumoniae by assessing morphology, host range, growth kinetics, physicochemical stability, and resistance frequency. Genomes were sequenced to confirm absence of lysogeny and virulence genes. Infection dynamics was visualized via fluorescence microscopy. Phage activity was tested across 60 different MDR K. pneumoniae clinical isolates, obtained from diverse sources such as blood, sputum, occult feces, urine etc.

Results

All six isolated phages were identified as novel dsDNA phages belonging to Caudoviricetes, with genome sizes ranging from 111 to 169 Kbp, devoid of virulence and AMR genes and demonstrating strong bacteriolytic activity. Growth kinetics indicated burst sizes varying from 12-148 PFU/infected cell. The phages displayed stability between 4-50°C, pH 4 -10 and sustained complete activity after lyophilization. More significantly, the phages and their cocktail combinations could effectively kill 93% of MDR K. pneumoniae clinical isolates.

Conclusion

These findings establish a panel of genetically safe, phenotypically diverse phages with broad and synergistic activity against MDR K. pneumoniae. The unique replication phenotypes and formulation stability highlight their potential for therapeutic development and deployment in clinical or resource-limited settings.