title: Delivery of the endolysin Cpl-1 by inhalation rescues mice with fatal pneumococcal pneumonia.
abstract: OBJECTIVE
  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.
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Jan M
authors: JM
authors: Doehn
authors: Katja
authors: K
authors: Fischer
authors: Katrin
authors: K
authors: Reppe
authors: Birgitt
authors: B
authors: Gutbier
authors: Thomas
authors: T
authors: Tschernig
authors: Andreas C
authors: AC
authors: Hocke
authors: Vincent A
authors: VA
authors: Fischetti
authors: Jutta
authors: J
authors: Löffler
authors: Norbert
authors: N
authors: Suttorp
authors: Stefan
authors: S
authors: Hippenstiel
authors: Martin
authors: M
authors: Witzenrath
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D058491:Bacterial Load; D001435:Bacteriophages / Q000201:enzymology*; D001688:Biological Products / Q000008:administration & dosage* / Q000302:isolation & purification; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000008:administration & dosage* / Q000302:isolation & purification; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D010450:Endopeptidases; C001143:endolysin
keywords: aerosolized; bacteriophage; enzybiotics; pneumococcus