Delivery of the endolysin Cpl-1 by inhalation rescues mice with fatal pneumococcal pneumonia

J Antimicrob Chemother. 2013 Sep;68(9):2111-7. doi: 10.1093/jac/dkt131. Epub 2013 Apr 30.


Objectives: Pneumonia is associated with a high morbidity and mortality worldwide. Streptococcus pneumoniae remains the most common cause of pneumonia, and pneumococcal antibiotic resistance is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci. We tested the hypothesis that a single dose of recombinant aerosolized Cpl-1 would rescue mice with severe pneumococcal pneumonia.

Methods: Female C57Bl/6 mice (aged 8-12 weeks) were transnasally infected with pneumococci. When severe pneumonia was established 24 h after infection, mice were treated with 25 μL of aerosolized Cpl-1. Survival was monitored for 10 days and the pulmonary and systemic bacterial burdens were assessed. Furthermore, cytokines were quantified in bronchoalveolar lavage fluid, and lung morphology was analysed histologically.

Results: The endolysin efficiently reduced pulmonary bacterial counts and averted bacteraemia. Although concentrations of inflammatory cytokines were increased shortly after Cpl-1 inhalation, mice recovered rapidly, as shown by increasing body weight, and inflammatory infiltrates resolved in the lungs, leading to a reduction in mortality of 80%.

Conclusions: Administration of Cpl-1 by inhalation may offer a new therapeutic perspective for the treatment of pneumococcal lung infection.

Keywords: aerosolized; bacteriophage; enzybiotics; pneumococcus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / isolation & purification
  • Bacterial Load
  • Bacteriophages / enzymology*
  • Biological Products / administration & dosage*
  • Biological Products / isolation & purification
  • Disease Models, Animal
  • Endopeptidases / administration & dosage*
  • Endopeptidases / isolation & purification
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia, Pneumococcal / drug therapy*
  • Streptococcus pneumoniae / drug effects*
  • Survival Analysis
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Biological Products
  • Endopeptidases
  • endolysin