机构：[a]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, Yunnan, China[b]Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China[c]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China[d]Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China[e]Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical College, Kunming 650032, Yunnan, China昆明医科大学附属第一医院云南省第一人民医院[f]Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai 201203, China[g]Kunming Institute of Zoology-The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China[h]Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuchang District, Jiangxia District, Wuhan 430071, China
The emergence of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa raises fears of untreatable infections and poses the greatest health threats. Antimicrobial peptides (AMPs) are regarded as the most ideal solution to this menace. In this study, a set of peptides was designed based on our previously reported peptide cathelicidin-BF-15, and the lead peptide ZY4, a cyclic peptide stabilized by a disulfide bridge with high stability in vivo (the half-life is 1.8 h), showed excellent activity against P. aeruginosa and A. baumannii, including standard and clinical multidrug-resistant (MDR) strains. ZY4 killed bacteria by permea-bilizing the bacterial membrane and showed low propensity to induce resistance, exhibited biofilm inhibition and eradication activities, and also killed persister cells. Notably, administration of ZY4 decreased susceptibility to lung infection by P. aeruginosa and suppressed dissemination of P. aeruginosa and A. baumannii to target organs in a mouse septicemia infection model. These findings identify ZY4 as an ideal candidate against MDR bacterial infections.
基金：
This work was supported by a National Natural
Science Foundation of China (NSFC) grant (21761142002), Chinese Academy of
Science grants (XDB31000000, SAJC201606, KGFZD-135-17-011, and KFJ-BRP-
008), and a Yunnan Province grant (2015HA023) to R.L. and a NSFC grant
(81770464), Chinese Academy of Science grants (XDA12040221 and Youth Innovation
Promotion Association [2017432]), and a National Key R&D Program
of China grant (2018YFC2000400) to Z.Z.
第一作者机构：[a]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, Yunnan, China[b]Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China[c]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China[d]Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
James Mwangi,Yizhu Yin,Gan Wang,et al.The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2019,116(52):26516-26522.doi:10.1073/pnas.1909585117.
APA：
James Mwangi,Yizhu Yin,Gan Wang,Min Yang,Ya Li...&Ren Lai.(2019).The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116,(52)
MLA：
James Mwangi,et al."The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116..52(2019):26516-26522
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