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.
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We thank Drs. Julie Sotsky and Anuradha Shelar, University of Louisville for contributing confirmatory data for select experiments and Dr. Paul B.M. Joyce, Concordia University, Montreal, Canada for critical reading of the manuscript. This work was funded by U.S. PHS grant R01DE17989 from the National Institute for Dental and Craniofacial Research . Institutional support from the University of Minnesota and University of Louisville Schools of Dentistry is gratefully acknowledged.