title: Activation of the complement system generates antibacterial peptides.
abstract: The complement system represents an evolutionary old and significant part of the innate immune system involved in protection against invading microorganisms. Here, we show that the anaphylatoxin C3a and its inactivated derivative C3a-desArg are antibacterial, demonstrating a previously unknown direct antimicrobial effect of complement activation. The C3a peptide, as well as functional epitopes in the sequence, efficiently killed the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and the Gram-positive Enterococcus faecalis. In mice, a C3a-derived peptide suppressed infection by Gram-positive Streptococcus pyogenes bacteria. Fluorescence and electron microscopy demonstrated that C3a binds to and induces breaks in bacterial membranes. C3a was also found to induce membrane leakage of liposomes. These findings provide an interesting link between the complement system and antimicrobial peptides, which are two important branches of innate immunity.
authors.affiliation: Department of Dermatology and Venereology, Lund University, Biomedical Center, Tornavägen 10, SE-221 84 Lund, Sweden.
authors.forename: Emma Andersson
authors.initials: EA
authors.lastname: Nordahl
authors.forename: Victoria
authors.initials: V
authors.lastname: Rydengård
authors.forename: Patrik
authors.initials: P
authors.lastname: Nyberg
authors.forename: D Patric
authors.initials: DP
authors.lastname: Nitsche
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D015169:Colony Count, Microbial; D003167:Complement Activation; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides