Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection
10.5847/wjem.j.1920-8642.2024.014
- Author:
Yangyang Guo
1
Author Information
1. Department of Intensive Care Medicine, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310021, China
- Publication Type:Journal Article
- Keywords:
Streptococcus pneumoniae;
Antimicrobial peptides;
Human α-defensin 5;
Infection
- From:
World Journal of Emergency Medicine
2024;15(1):28-34
- CountryChina
- Language:English
-
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.
