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

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. Female C57Bl/6 mice (aged 812 weeks) were transnasally infected with pneumococci. When severe pneumonia was established 24 h after infection, mice were treated with 25 L 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. 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. Administration of Cpl-1 by inhalation may offer a new therapeutic perspective for the treatment of pneumococcal lung infection.