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Inhalable bacteriophage endolysins: a novel therapeutic strategy for drug-resistant bacterial pulmonary infections -

Dongyan Ding1,2, Hailing Duan2, Fang Zhang1

  • 1Department of Respiratory and Critical Care Medicine, Jiangbei Campus of The First Affiliated Hospital of Army Medical University(No. 958 Hospital of PLA Army), Chongqing, China.

Annals of Medicine
|June 27, 2026
PubMed
Abstract

Insights

Bacteriophage endolysins offer a novel approach to combat multidrug-resistant (MDR) pulmonary infections. Inhaled endolysins show promise as an alternative or adjunct therapy, effectively treating pneumonia with minimal toxicity.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Multidrug-resistant (MDR) bacterial pulmonary infections, particularly hospital-acquired pneumonia, present a critical global health challenge.
  • The development pipeline for new antibiotics is stagnant, necessitating novel therapeutic strategies.

Purpose of the Study:

  • This review explores the potential of bacteriophage endolysins as a therapeutic agent against major multidrug-resistant respiratory pathogens.
  • The focus is on their mechanisms, synergistic effects with antibiotics, and efficacy, especially when delivered via inhalation.

Main Methods:

  • Review of recent scientific literature on bacteriophage endolysins.
  • Analysis of endolysin activity against key MDR respiratory pathogens: Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae.
  • Evaluation of inhalation delivery systems for pulmonary administration.

Main Results:

  • Endolysins exhibit potent, species-specific lytic activity against a wide range of MDR bacteria with a low risk of resistance development.
  • Optimized inhalation delivery allows high local lung concentrations of endolysins, effectively clearing pathogens in animal pneumonia models with reduced systemic toxicity.
  • Direct pulmonary delivery circumvents systemic administration challenges, improving therapeutic outcomes.

Conclusions:

  • Bacteriophage endolysins represent a significant advancement in treating drug-resistant bacterial lung infections.
  • Their rapid lytic action, synergistic potential with antibiotics, and suitability for inhalable formulations position them as valuable therapeutic options.
  • Further development of stabilization and large-scale production, alongside optimized inhalation systems, could revolutionize respiratory infection treatment.
Keywords:
Bacteriophage endolysinsantimicrobial agentdrug-resistant bacteriadrug-resistant bacterial pulmonary infections

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