Lysine substitutions convert a bacterial-agglutinating peptide into a bactericidal peptide that retains anti-lipopolysaccharide activity and low hemolytic activity

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• 作者：Mahsa Abdolhosseini¹ ; ^{abd_mahsa@yahoo.com} ; Seshagiri R. Nandula ^{snandula@umn.edu} ; Jonathan Song ^{songx095@umn.edu} ; Helmut Hirt ^{hirtx001@umn.edu} ; Sven-Ulrik Gorr ; ^{sugorr@umn.edu}
• 关键词：BPI ; bactericidal/permeability-increasing protein ; CFU ; colony forming units ; LPS ; lipopolysaccharide ; MIC ; minimum inhibitory concentration ; OD ; optical density ; PBS ; phosphate-buffered saline ; PLUNC ; palate ; lung ; nasal epithelium clone ; PSP ; parotid se
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：June, 2012
• 卷：35
• 期：2
• 页码：231-238
• 文件大小：755 K

摘要

GL13NH2 is a bacteria-agglutinating peptide derived from the sequence of the salivary protein parotid secretory protein (PSP, BPIFA2, SPLUNC2, C20orf70). The peptide agglutinates both Gram negative and Gram positive bacteria, and shows anti-lipopolysaccharide activity in vitro and in vivo. However, GL13NH2 does not exhibit bactericidal activity. To generate a more cationic peptide with potential bactericidal activity, three amino acid residues were replaced with lysine residues to generate the peptide GL13K. In this report, the antibacterial and anti-inflammatory activities of GL13K were characterized. GL13K had lost the ability to agglutinate bacteria but gained bactericidal activity. Substitution of individual amino acids in GL13K with alanine did not restore bacterial agglutination. GL13K was bactericidal against Pseudomonas aeruginosa, Streptococcus gordonii and Escherichia coli but not Porphyromonas gingivalis. Unlike the agglutinating activity of GL13NH2, the bactericidal activity of GL13K against P. aeruginosa was retained in the presence of saliva. Both GL13NH2 and GL13K exhibited anti-lipopolysaccharide activity. In GL13K, this activity appeared to depend on a serine hydroxyl group. GL13K protected mice from lipopolysaccharide-induced sepsis and the peptide exhibited a low level of hemolysis, suggesting that it may be suitable for in vivo application.