Chemotherapy with Phage Lysins Reduces Pneumococcal Colonization of the Respiratory Tract [PublishAheadOfPrint]

Bacteriophage-encoded lytic enzymes, also named lysins, or enzybiotics, are efficient agents to kill bacterial pathogens. Colonization of the respiratory tract by Streptococcus pneumoniae is a prerequisite for the establishment of the infection process. Hence, we have evaluated the antibacterial activity of three different lysins against pneumococcal colonization using human nasopharyngeal and lung epithelial cells as well as a mouse model of nasopharyngeal colonization. The lysins tested were the wild type Cpl-1, the engineered Cpl-7S, and the chimera Cpl-711. Moreover, we have included amoxicillin as a comparator antibiotic. Human epithelial cells were infected with three different multidrug-resistant clinical isolates of S. pneumoniae followed by a single dose of the corresponding lysin. The antimicrobial activity of these lysins was also evaluated using a mouse nasopharyngeal carriage model. Exposure of infected epithelial cells to Cpl-7S did not result in the killing of any of the pneumococcal strains investigated. However, treatment with Cpl-1 or Cpl-711 increased the killing of S. pneumoniae adhered to both types of human epithelial cells with Cpl-711 being more effective than Cpl-1, at sub-inhibitory concentrations. In addition, treatment with amoxicillin had no effect reducing the carrier state whereas mice treated by the intranasal route with Cpl-711 showed significantly reduced nasopharyngeal colonization with no detection of bacterial load in 20-40% of the mice. This study indicates that Cpl-1 and Cpl-711 lysins might be promising antimicrobial candidates for therapy against pneumococcal colonization.

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