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

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

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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 fiuid 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.

Streptococcus pneumoniaeAntimicrobial peptidesHuman α-defensin 5Infection

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

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Department of Intensive Care Medicine,Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University,Hangzhou 310021,China

National Children's Regional Medical Center,National Clinical Research Center for Child Health,Children's Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China

Department of Spleen and Stomach Diseases,Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University,Hangzhou 310021,China

Department of Ultrasonic Medicine,the First Affiliated Hospital of Ningbo University,Ningbo 315010,China

Department of Anesthesiology,the First Affiliated Hospital of Ningbo University,Ningbo 315010,China

Zhejiang University School of Medicine,Hangzhou 310058,China

The First People's Hospital of Yuexi County,Yuexi 616650,China

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国家自然科学基金Zhejiang Provincial Basic Public Welfare Research Program of Zhejiang ProvinceZhejiang Medicine and Health Science and Technology Project宁波市自然科学基金

82072148LGF21H1500022022RC245&2023KY2552023J134

2024

10.5847/wjem.j.1920-8642.2024.014

世界急诊医学杂志(英文)
浙江大学,浙江大学医学院附属第二医院

世界急诊医学杂志(英文)

ISSN：1920-8642
年,卷(期)：2024.15(1)
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