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A novel chemosynthetic peptide with beta-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model

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机构: [1]Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58203 USA [2]Yunnan Univ, Sch Life Sci, Lab Biochem & Mol Biol, Kunming, Peoples R China [3]Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610064, Peoples R China [4]Nanos, Inst Bioengn & Nanotechnol, Singapore, Singapore [5]Zhejiang Univ, Affiliated Hosp 1, Coll Med, Program Innovat Canc Therapeut, Hangzhou 310003, Zhejiang, Peoples R China
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关键词: bacterial pathogenesis inflammatory cytokines infectious diseases bactericidal activity antimicrobial peptides STAT3/JAK signaling transduction

摘要:
Klebsiella pneumoniae (Kp) is one of the most common pathogens in nosocomial infections and is increasingly becoming multiple drug resistant. However, the molecular pathogenesis of Kp in causing tissue injury and dysregulated host defense remains elusive, further dampening the development of novel therapeutic measures. We have previously screened a series of synthetic antimicrobial beta-sheet forming peptides and identified a peptide (IRIKIRIK; ie, IK8L) with a broad range of bactericidal activity and low cytotoxicity in vitro. Here, employing an animal model, we investigated the antibacterial effects of IK8L in acute infection and demonstrated that peritoneal injection of IK8L to mice down-regulated inflammatory cytokines, alleviated lung injury, and importantly, decreased mortality compared to sham-injected controls. In addition, a math model was used to evaluate in vivo imaging data and predict infection progression in infected live animals. Mechanistically, IK8L can kill Kp by inhibiting biofilm formation and modulating production of inflammatory cytokines through the STAT3/JAK signaling both in vitro and in vivo. Collectively, these findings reveal that IK8L may have potential for preventing or treating Kp infection.

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出版当年[2015]版:
大类 | 2 区 工程技术
小类 | 2 区 药学 3 区 纳米科技
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 纳米科技
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出版当年[2014]版:
Q1 PHARMACOLOGY & PHARMACY Q2 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版:
Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58203 USA [2]Yunnan Univ, Sch Life Sci, Lab Biochem & Mol Biol, Kunming, Peoples R China
通讯作者:
通讯机构: [1]Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58203 USA [4]Nanos, Inst Bioengn & Nanotechnol, Singapore, Singapore
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