期刊
FASEB JOURNAL
卷 24, 期 4, 页码 1015-1022出版社
WILEY
DOI: 10.1096/fj.09-145474
关键词
dendrimers; antibacterial; cystic fibrosis; gramnegative bacteria; LPS
资金
- Fondazione Italiana per la Ricerca sulla Fibrosi cistica [FFC 14/2009]
We describe the nonnatural antimicrobial peptide KKIRVRLSA (M33) and its capacity to neutralize LPS-induced cytokine release, preventing septic shock in animals infected with bacterial species of clinical interest. M33 showed strong resistance to proteolytic degradation when synthesized in tetra-branched form with 4 peptides linked by a lysine core, making it suitable for use in vivo. HPLC and mass spectrometry demonstrated its stability in serum beyond 24 h. M33 was found to be very selective for gram-negative bacteria. Minimal inhibitory concentration (MIC) ranged from 0.3 to 3 mu M for multidrug resistant clinical isolates of several pathogenic species, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. M33 neutralized LPS derived from P. aeruginosa and K. pneumoniae, and prevented TNF-alpha release from LPS-activated macrophages, with an EC50 of 3.8e-8 M and 2.8e-7 M, respectively, as detected by sandwich ELISA. M33 activity was also tested in sepsis animal models. It averted septic shock symptoms due to Escherichia coli and P. aeruginosa in doses compatible with clinical use (5-25 mg/kg). These properties make tetrabranched M33 peptide a good candidate for the development of a new antibacterial drug.-Pini, A., Falciani, C., Mantengoli, E., Bindi, S., Brunetti, J., Iozzi, S., Rossolini, G. M., Bracci, L. A novel tetrabranched antimicrobial peptide that neutralizes bacterial lipopolysaccharide and prevents septic shock in vivo. FASEB J. 24, 1015-1022 (2010). www.fasebj.org
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据