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

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

机构地区：[1]Department of Intensive Care Medicine,Hangzhou Traditional Chinese Medicine Hospital Affi liated to Zhejiang Chinese Medical University,Hangzhou 310021,China [2]National Children’s Regional Medical Center,National Clinical Research Center for Child Health,Children’s Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China [3]Department of Spleen and Stomach Diseases,Hangzhou Traditional Chinese Medicine Hospital Affi liated to Zhejiang Chinese Medical University,Hangzhou 310021,China [4]Department of Ultrasonic Medicine,the First Affi liated Hospital of Ningbo University,Ningbo 315010,China [5]Department of Anesthesiology,the First Affi liated Hospital of Ningbo University,Ningbo 315010,China [6]Zhejiang University School of Medicine,Hangzhou 310058,China [7]The First People’s Hospital of Yuexi County,Yuexi 616650,China

出　　处：《World Journal of Emergency Medicine》2024年第1期28-34,共7页世界急诊医学杂志（英文）

基　　金：supported by the National Natural Science Foundation of China(82072148);Zhejiang Provincial Basic Public Welfare Research Program of Zhejiang Province(LGF21H150002);Zhejiang Medicine and Health Science and Technology Project(2022RC245&2023KY255);Ningbo Municipal Natural Science Foundation(2023J134).

摘　　要：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 humanα-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 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),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 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

关 键 词：Streptococcus pneumoniae Antimicrobial peptides Humanα-defensin 5 INFECTION 

分 类 号：R563.1[医药卫生—呼吸系统]