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<p>AMR has become a critical health-care challenge primarily driven by carbapenem-resistant Gram-negative infections, and it is projected to worsen sharply by 2050, especially in South Asia, unless major interventions are implemented. One of the major contributors to this burden is <i>Klebsiella pneumoniae.</i> The WHO has categorised carbapenem-resistant <i>K. pneumoniae</i> as a critical priority pathogen, and the current prevalence of carbapenem-resistant hypervirulent <i>K</i>. <i>pneumoniae</i> has raised concerns about potential future pandemics. The bacteria can mediate the transfer of resistance from environmental to clinical strains. Moreover, biofilm-associated infections caused by multidrug-resistant <i>K. pneumoniae</i> exacerbate healthcare challenges, particularly in hospital-acquired infections associated with medical devices such as catheters and implants. Amid escalating antibiotic failures, bacteriophages have re-emerged from the pre-antibiotic era as a new-age therapeutic alternative to combat drug-resistant bacterial infections. We report <i>SAKp26</i>.2, a novel <i>Autographiviridae</i> phage isolated from hospital sewage, which acts as an effective antibacterial and antibiofilm agent against several clinical, drug-resistant <i>K. pneumoniae</i> strains. Combination treatment of <i>SAKp26.2</i> with antibiotics resulted in a significant delay in the emergence of treatment resistance compared to monotherapy, supporting its potential as a phage-antibiotic combination therapeutic. The phage has a genome size of 41,467&#xa0;bp and lacks any virulence or antibiotic resistance genes. <i>SAKp26.2</i> is a strong depolymerase-producing phage and is equipped with other critical lysis-associated enzymes. A rapid clearance of biofilm biomass was observed, with a 99% reduction in viable cell count within 4&#xa0;h post-bacteriophage treatment. Additionally, our study illustrates an association between efficiency of plating and kill-kinetics performance, reflecting how phage replication efficiency within a host population may influence the epidemiological spread of infection. Notably, the phage also showed significant biofilm clearance from urinary tract catheters, indicating potential biomedical applications. Overall, this study integrates fundamental phage biology with a clinically relevant scenario, bridging the gap between bench and bedside.</p> Graphical Abstract <p></p>

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Genomic characterization and evaluation of a novel Autographiviridae phage SAKp26.2 against in vitro urinary catheter-associated biofilms of drug-resistant Klebsiella pneumoniae

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月16日

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  • Aafreen Aafreen,
  • Sambuddha Chakraborty,
  • Deepangkar Chisim Sangma,
  • Anusha Jatley,
  • Ram Karan,
  • Ashwini Chauhan

摘要

AMR has become a critical health-care challenge primarily driven by carbapenem-resistant Gram-negative infections, and it is projected to worsen sharply by 2050, especially in South Asia, unless major interventions are implemented. One of the major contributors to this burden is Klebsiella pneumoniae. The WHO has categorised carbapenem-resistant K. pneumoniae as a critical priority pathogen, and the current prevalence of carbapenem-resistant hypervirulent K. pneumoniae has raised concerns about potential future pandemics. The bacteria can mediate the transfer of resistance from environmental to clinical strains. Moreover, biofilm-associated infections caused by multidrug-resistant K. pneumoniae exacerbate healthcare challenges, particularly in hospital-acquired infections associated with medical devices such as catheters and implants. Amid escalating antibiotic failures, bacteriophages have re-emerged from the pre-antibiotic era as a new-age therapeutic alternative to combat drug-resistant bacterial infections. We report SAKp26.2, a novel Autographiviridae phage isolated from hospital sewage, which acts as an effective antibacterial and antibiofilm agent against several clinical, drug-resistant K. pneumoniae strains. Combination treatment of SAKp26.2 with antibiotics resulted in a significant delay in the emergence of treatment resistance compared to monotherapy, supporting its potential as a phage-antibiotic combination therapeutic. The phage has a genome size of 41,467 bp and lacks any virulence or antibiotic resistance genes. SAKp26.2 is a strong depolymerase-producing phage and is equipped with other critical lysis-associated enzymes. A rapid clearance of biofilm biomass was observed, with a 99% reduction in viable cell count within 4 h post-bacteriophage treatment. Additionally, our study illustrates an association between efficiency of plating and kill-kinetics performance, reflecting how phage replication efficiency within a host population may influence the epidemiological spread of infection. Notably, the phage also showed significant biofilm clearance from urinary tract catheters, indicating potential biomedical applications. Overall, this study integrates fundamental phage biology with a clinically relevant scenario, bridging the gap between bench and bedside.

Graphical Abstract