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.
基金:
Flight Attendant Medical Research Institute (FAMRI) [103007]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AI109317-01A1, AI101973-01, AI097532-01A1]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31260276, 30760057, 30960091]; Yunnan Province Science and Technology Innovation Team [2011CI123, 2012Z053, 2012S208]; Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)Agency for Science Technology & Research (ASTAR)
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
推荐引用方式(GB/T 7714):
Tan Shirui,Gan Changpei,Li Rongpeng,et al.A novel chemosynthetic peptide with beta-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model[J].INTERNATIONAL JOURNAL OF NANOMEDICINE.2015,10:1045-1059.doi:10.2147/IJN.S73303.
APA:
Tan, Shirui,Gan, Changpei,Li, Rongpeng,Ye, Yan,Zhang, Shuang...&Wu, Min.(2015).A novel chemosynthetic peptide with beta-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model.INTERNATIONAL JOURNAL OF NANOMEDICINE,10,
MLA:
Tan, Shirui,et al."A novel chemosynthetic peptide with beta-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model".INTERNATIONAL JOURNAL OF NANOMEDICINE 10.(2015):1045-1059