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<p>This review provides a critical analysis of the potential applications of phage therapy and genetic engineering in addressing antimicrobial-resistant bacterial infections caused by <i>Klebsiella</i> spp. It highlights the significance of phage banks in facilitating the characterization and standardization of clinical isolates, thereby supporting the development of targeted therapeutic strategies. Bacterial resistance mechanisms, including receptor modifications, efflux pump alterations, and conformational mutations, present considerable challenges; however, they also inform approaches such as phage engineering and the formulation of phage cocktails designed to overcome resistance. The combined use of phages and antibiotics can produce synergistic effects, enhancing bacterial eradication and mitigating the emergence of resistance. Recent advances in genetic modification techniques aim to improve phage safety, reduce immunogenicity, and increase therapeutic efficacy, exemplified by the modification of lysogenic phages to minimize transduction risks. Additionally, the co-evolutionary dynamics between bacteria and phages enable the optimization of phage-receptor specificity, which may reduce bacterial virulence and restore antibiotic susceptibility. Collectively, these strategies offer promising avenues for the development of innovative, precision antimicrobial interventions in the context of escalating resistance.</p>

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Phage therapy for antimicrobial-resistant Klebsiella spp. infections: a review of mechanisms, synergies, and clinical potential

  • 期刊论文

  • 发表日期：

    2025年10月13日

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  • Giulia Condas,
  • Maria Eduarda Xavier Pedroso,
  • Sheila Alexandra Belini Nishiyama,
  • Tiago Tognolli de Almeida,
  • Marcos Pileggi,
  • Luiz Ricardo Olchanheski

摘要

This review provides a critical analysis of the potential applications of phage therapy and genetic engineering in addressing antimicrobial-resistant bacterial infections caused by Klebsiella spp. It highlights the significance of phage banks in facilitating the characterization and standardization of clinical isolates, thereby supporting the development of targeted therapeutic strategies. Bacterial resistance mechanisms, including receptor modifications, efflux pump alterations, and conformational mutations, present considerable challenges; however, they also inform approaches such as phage engineering and the formulation of phage cocktails designed to overcome resistance. The combined use of phages and antibiotics can produce synergistic effects, enhancing bacterial eradication and mitigating the emergence of resistance. Recent advances in genetic modification techniques aim to improve phage safety, reduce immunogenicity, and increase therapeutic efficacy, exemplified by the modification of lysogenic phages to minimize transduction risks. Additionally, the co-evolutionary dynamics between bacteria and phages enable the optimization of phage-receptor specificity, which may reduce bacterial virulence and restore antibiotic susceptibility. Collectively, these strategies offer promising avenues for the development of innovative, precision antimicrobial interventions in the context of escalating resistance.