Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that causes bacterial pneumonia.However, with increasing bacterial resistance, there is an urgent need to develop new drugs to treat S. pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid (ND-C14) is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of human α-defensin 5 (HD5) via an amide bond.However, it is unclear whether ND-C14 is effective against lung infections caused by S. pneumoniae. METHODS:In vitro, three groups were established, including the control group, and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S. pneumoniae.The morphological changes of S. pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo, mice were divided into sham, vehicle, and ND-C14 treatment groups.Mice in the sham group were treated with 25 μL of phosphate-buffered saline (PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25 μL of bacterial suspension with 2×10 8 CFU/mL (total bacterial count: 5×10 6 CFU), and then the mice were given 25 μL PBS or intratracheally injected with 25 μL of ND-C14 (including 20 μg or 50 μg), respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fl uid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S. pneumoniae. RESULTS:Compared with HD5, ND-C14 had a better bactericidal eff ect against S. pneumoniae because of its stronger ability to destroy the membrane structure of S. pneumoniae in vitro.In vivo, ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S. pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover, ND-C14 had a membrane permeation eff ect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration. CONCLUSION:The ND-C14 may improve bactericidal eff ects on S. pneumoniae both in vitro and in vivo.