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

IF 2.6 3区医学 Q1 EMERGENCY MEDICINE

World journal of emergency medicine Pub Date : 2024-01-01 DOI:10.5847/wjem.j.1920-8642.2024.014

Yangyang Guo, Yaqi Sun, Hongxia Wu, Jian Lu, Yuan Lin, Jiaqing Zhu, Meihong Lai, Meiqi Zhang, Jun Wang, Jungang Zheng

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引用次数: 0

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.

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纳米抗菌肽 ND-C14 对肺炎链球菌感染的保护作用及其机理。

背景：肺炎链球菌（S. pneumoniae）是引起细菌性肺炎的常见病原体。然而，随着细菌耐药性的增加，迫切需要开发治疗肺炎链球菌感染的新药物。含 14 碳饱和脂肪酸的纳米抗菌肽（ND-C14）是通过酰胺键修饰人α-防御素 5（HD5）C 端肉豆蔻酸而设计的一种新型纳米抗菌肽。然而，ND-C14 对肺炎双球菌引起的肺部感染是否有效尚不清楚：方法：在体外设立三个组，包括对照组、HD5 和 ND-C14 治疗组。采用虚拟菌落计数法评估 HD5 和 ND-C14 对肺炎双球菌的抗菌活性。用扫描电子显微镜观察经 HD5 或 ND-C14 处理的肺炎双球菌的形态学变化。在体内，小鼠被分为假治疗组、药物治疗组和 ND-C14 治疗组。假组小鼠用 25 μL 磷酸盐缓冲盐水（PBS）处理。给载体组和 ND-C14 治疗组的小鼠气管内灌注 25 μL 含有 2×108 CFU/mL 的细菌悬液（细菌总数：5×106 CFU），然后分别给小鼠注射 25 μL PBS 或气管内注射 25 μL ND-C14（包括 20 μg 或 50 μg）。评估了药物组和 ND-C14 治疗组的存活率。对血液和支气管肺泡灌洗液中的细菌量进行计数。对小鼠的肺组织学进行评估。碘化丙啶摄取试验用于明确 ND-C14 对肺炎双球菌的破坏作用：结果：与 HD5 相比，ND-C14 对肺炎双球菌的杀菌效果更好，因为它在体外破坏肺炎双球菌膜结构的能力更强。在体内，ND-C14能明显延缓肺炎双球菌感染小鼠的死亡时间，提高其存活率。ND-C14 可减少细菌负荷和肺组织损伤。此外，ND-C14对肺炎双球菌具有膜渗透作用，其破坏能力随ND-C14浓度的增加而增强：结论：ND-C14 可在体外和体内提高对肺炎双球菌的杀菌效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World journal of emergency medicine EMERGENCY MEDICINE-

CiteScore

2.50

自引率

28.60%

发文量

671

期刊介绍： The journal will cover technical, clinical and bioengineering studies related to multidisciplinary specialties of emergency medicine, such as cardiopulmonary resuscitation, acute injury, out-of-hospital emergency medical service, intensive care, injury and disease prevention, disaster management, healthy policy and ethics, toxicology, and sudden illness, including cardiology, internal medicine, anesthesiology, orthopedics, and trauma care, and more. The journal also features basic science, special reports, case reports, board review questions, and more. Editorials and communications to the editor explore controversial issues and encourage further discussion by physicians dealing with emergency medicine.