数字农科院2.0

Functional characterisation and modification of a novel Kunitzin peptide for use as an anti-trypsin antimicrobial peptide against drug-resistant Escherichia coli

文献类型： 外文期刊

作者： Wang Z.;Ding W.;Shi D.;Chen X.;Ma C.;Jiang Y.;Wang T.;Chen T.;Shaw C.;Wang L.;Zhou M.

作者机构：

关键词： Anti-endotoxin;Antimicrobial peptides;Drug resistance;Peptide modification;Proteolytic tolerance

期刊名称： Biochemical Pharmacology

ISSN： 0006-2952

年卷期： 2024 年 229 卷

页码：

收录情况： SCIE（2024版）

摘要： In recent decades, antimicrobial peptides (AMPs) have emerged as highly promising candidates for the next generation of antibiotic agents, garnering significant attention. Although their potent antimicrobial activities and ability to combat drug resistance make them stand out among alternative agents, their poor stability has presented a great challenge for further development. In this work, we report a novel Kunitzin AMP, Kunitzin-OL, from the frog Odorrana lividia, exhibiting dual antimicrobial and anti-trypsin activities. Through functional screening and comparison with previously reported Kunitzin peptides, we serendipitously discovered a unique motif (−KVKF-) and unveiled its crucial role in the antibacterial functions of Kunitzin-OL by modifying it through motif removal and duplication. Among the designed derivatives, peptides 4 and 8 demonstrated remarkable antimicrobial activities and low cytotoxicity, with high therapeutic index (TI) values (TI4 = 20.8, TI8 = 20.8). Furthermore, they showed potent antibacterial efficacy against drug-resistant Escherichia coli strains and exhibited lipopolysaccharide (LPS)-neutralising activity, effectively alleviating LPS-induced inflammatory responses. Overall, our findings provide a new short motif for designing effective AMP drugs and highlight the potential of the Kunitztin trypsin inhibitory loop as a valuable motif for the design of AMPs with enhancing proteolytic stability. © 2024 The Author(s)

分类号：

  • 相关文献

[1]Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms. Xinze Liu,Daning Shi,Shiya Cheng,Xiaoling Chen,Chengbang Ma,Yangyang Jiang,Tao Wang,Tianbao Chen,Chris Shaw,Lei Wang,Mei Zhou. 2024

[2]Expression and characterization of recombinant gallinacin-9 and gallinacin-8 in Escherichia coli. Ma, De-ying,Shan, An-shan,Liu, Sheng-wang,Han, Zong-xi,Li, Yi-jin.

[3]Resistance to drug by different isolates Trypanosoma evansi in China. Zhou, JL,Shen, J,Liao, DJ,Zhou, YZ,Lin, JJ. 2004

[4]Changes in antimicrobial resistance among Salmonella enterica subspecies enterica serovar Pullorum isolates in China from 1962 to 2007. Pan, Zhiming,Wang, Xiaoquan,Zhang, Xiaoming,Geng, Shizhong,Chen, Xiang,Pan, Weijuan,Cong, Qiuxia,Jiao, Xinan,Liu, Xiufan,Liu, Xuexian.

[5]Prevalence and Antimicrobial Resistance of Salmonella enterica Serovar Indiana in China (1984-2016). Gong, J.,Gong, J.,Wang, C.,Kelly, P.,Wang, C.,Wang, C..

[6]Characterization of avian pathogenic Escherichia coli isolated in eastern China. Dou, Xinhong,Gong, Jiansen,Xu, Ming,Shen, Haiyu,Zhang, Di,Liu, Jiasheng,Zou, Jianmin,Dou, Xinhong,Gong, Jiansen,Shen, Haiyu,Zou, Jianmin,Han, Xiangan,Zhuang, Linlin. 2016

[7]The SAR and action mechanisms of autophagy inhibitors that eliminate drug resistance. Ye W.,Fan C.,Fu K.,Wang X.,Lin J.,Nian S.,Liu C.,Zhou W.. 2022

[8]A Recombinase Polymerase Amplification-Coupled Cas12a Mutant-Based Module for Efficient Detection of Streptomycin-Resistant Mutations in Mycobacterium tuberculosis. Peng Liu,Xinjie Wang,Juan Liang,Qian Dong,Jinping Zhang,Dongxin Liu,Shuai Wang,Jing Bi,Wenqi Liu,Zhaoqin Wang,Liang Chen,Lei Liu,Xingxu Huang,Guoliang Zhang. 2022

[9]Rapid and Sensitive Diagnosis of Drug-Resistant FLT3-F691L Mutation by CRISPR Detection. Yin Liu,Yanling Chen,Shisheng Huang,Xiaodong Ma,Xingxu Huang,Xinjie Wang,Fuling Zhou. 2021

[10]Molecular characterization of glyceraldehyde-3-phosphate dehydrogenase from Eimeria tenella. Huang, Wenhao,Zhu, Shunhai,Chen, Ting,Zhao, Qiping,Dong, Hui,Huang, Bing,Yao, Yawen,Liu, Zhan,Yu, Yu,Han, Hongyu. 2022

[11]Editorial: Foodborne Enterobacteriaceae of Animal Origin. Fangkun Wang,Wanjiang Zhang,Dongyan Niu. 2021

[12]Label-free quantitative proteomic analysis of ethanamizuril-resistant versus -sensitive strains of Eimeria tenella. Peipei Cheng,Chunmei Wang,Lifang Zhang,Chenzhong Fei,Yingchun Liu,Mi Wang,Keyu Zhang,Xiaoyang Wang,Feng Gu,Feiqun Xue. 2022

[13]Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line derived from a Chinese patient. Miao X.,Hu J.,Chai C.,Tang H.,Zhao Z.,Luo W.,Zhou W.,Xu H.. 2022

[14]Interplay Between The Phenotype And G.enotype, And Efflux Pumps I n Drug-Resistant Strains Of Riemerella Anatipestifer. Chen, QW,Gong, XW,Zheng, FY,Ji, G,Li, SD,Stipkovits, L,Szathmary, S,Liu, YS. 2018

[15]Tumor-Penetrating and Mitochondria-Targeted Drug Delivery Overcomes Doxorubicin Resistance in Lung Cancer. Zhou, Meng-Xue,Zhang, Jia-Yu,Cai, Xiao-Meng,Dou, Rui,Ruan, Li-Fo,Yang, Wen-Jiang,Lin, Wen-Chu,Chen, Jun,Hu, Yi. 2022

[16]Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line, ICC-X3. Xu, Hao,Luo, Wei,Zhao, Zhenjie,Miao, Xin,Chai, Changpeng,Hu, Jinjing,Tang, Huan,Zhang, Hui,Zhou, Wence. 2023

[17]Editorial: Antimicrobial resistance: agriculture, environment and public health within One Health framework. Tao Li,Haihong Hao,Xiaolin Hou,Jiang Xia. 2023

[18]Distinct non-synonymous mutations in cytochrome b highly correlate with decoquinate resistance in apicomplexan parasite Eimeria tenella. Zhenkai Hao,Junmin Chen,Pei Sun,Linlin Chen,Yuanyuan Zhang,Wenxuan Chen,Dandan Hu,Feifei Bi,Zhenyan Han,Xinming Tang,Jingxia Suo,Xun Suo,Xianyong Liu. 2023

[19]Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance. Pan Lei,Wenzhou Wang,Marisela Sheldon,Yutong Sun,Fan Yao,Li Ma. 2023

[20]Genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas veronii isolated from farmed largemouth bass (Micropterus salmoides) in the main aquaculture regions of China. Qikai Chen,Yunfei Xing,Yan Lei,Guixiang Tong,Xiaobu Lin,Pengcheng He,Shaolin Tang,Feifei Zheng,Hui Zeng,Xinxian Wei,Yong An Zhang,Yang Zhou. 2024

作者其他论文 更多>>