Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach

作     者：Xiaoyan Zhang Shan Li Haihua Luo Shuyue He Huangda Yang Lei Li Tian Tian Qizheng Han Jiacong Ye Chenyang Huang Aihua Liu Yong Jiang 

作者机构：Guangdong Provincial Key Laboratory of ProteomicsState Key Laboratory of Organ Failure ResearchDepartment of PathophysiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Respiratory and Critical Care MedicineNanfang HospitalSouthern Medical UniversityGuangzhouChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2022年第7卷第8期

页      面：3054-3068页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by grants from the NSFC-Guangdong Joint Foundation of China(U1601225) the National Natural Science Foundation of China(81671965 and 82130063) Special Support Plan for Outstanding Talents of Guangdong Province(2019JC05Y340) Guangdong Provincial Science and Technology Project(2016A020216015) 

主　　题：inhibited organs strain 

摘      要：Effectively killing pathogenic bacteria is key for the treatment of *** various anti-infective drugs have been used for the treatment of sepsis,the therapeutic effect is largely limited by the lack of a specific bacterium-targeting delivery *** study aimed to develop antibacterial peptides that specifically target pathogenic bacteria for the treatment of *** lethal bacterial strain Escherichia coli MSI001 was isolated from mice of a cecal ligation and puncture(CLP)model and was used as a target to screen bacterial binding heptapeptides through an integrative bioinformatics approach based on phage display technology and high-throughput sequencing(HTS).Heptapeptides binding to *** MSI001 with high affinity were acquired after normalization by the heptapeptide frequency of the library.A representative heptapeptide VTKLGSL(VTK)was selected for fusion with the antibacterial peptide LL-37 to construct the specific-targeting antibacterial peptide *** found that,in comparison with LL37,VTK-LL37 showed prominent bacteriostatic activity and an inhibitive effect on biofilm formation in *** vivo experiments demonstrated that VTK-LL37 significantly inhibited bacterial growth,reduced HMGB1 expression,alleviated lesions of vital organs and improved the survival of mice subjected to CLP ***,membrane DEGP and DEGQ were identified as VTKbinding proteins by proteomic *** study provides a novel strategy for targeted pathogen killing,which is helpful for the treatment of sepsis in the era of precise medicine.