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

doi:10.5847/wjem.j.1920-8642.2024.014

Abstract

Abstract:

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 2×10⁸ CFU/mL (total bacterial count: 5×10⁶ 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 fluid were counted. The lung histology of the mice was assessed. A propidium iodide uptake assay was used to clarify the destructive effect of ND-C14 against S. pneumoniae.
RESULTS: Compared with HD5, ND-C14 had a better bactericidal effect 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 effect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration.
CONCLUSION: The ND-C14 may improve bactericidal effects on S. pneumoniae both in vitro and in vivo.

Key words: Streptococcus pneumoniae, Antimicrobial peptides, Human α-defensin 5, Infection

Yangyang Guo, Yaqi Sun, Hongxia Wu, Jian Lu, Yuan Lin, Jiaqing Zhu, Meihong Lai, Meiqi Zhang, Jun Wang, Jungang Zheng. Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection[J]. World Journal of Emergency Medicine, 2024, 15(1): 28-34.

Figures/Tables 3

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