title: Antimicrobial activity of native and synthetic surfactant protein B peptides.
abstract: Surfactant protein B (SP-B) is secreted into the airspaces with surfactant phospholipids where it reduces surface tension and prevents alveolar collapse at end expiration. SP-B is a member of the saposin-like family of proteins, several of which have antimicrobial properties. SP-B lyses negatively charged liposomes and was previously reported to inhibit the growth of Escherichia coli in vitro; however, a separate study indicated that elevated levels of SP-B in the airspaces of transgenic mice did not confer resistance to infection. The goal of this study was to assess the antimicrobial properties of native SP-B and synthetic peptides derived from the native peptide. Native SP-B aggregated and killed clinical isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and group B streptococcus by increasing membrane permeability; however, SP-B also lysed RBC, indicating that the membranolytic activity was not selective for bacteria. Both the antimicrobial and hemolytic activities of native SP-B were inhibited by surfactant phospholipids, suggesting that endogenous SP-B may not play a significant role in alveolar host defense. Synthetic peptides derived from native SP-B were effective at killing both Gram-positive and Gram-negative bacteria at low peptide concentrations (0.15-5.0 microM). The SP-B derivatives selectively lysed bacterial membranes and were more resistant to inhibition by phospholipids; furthermore, helix 1 (residues 7-22) retained significant antimicrobial activity in the presence of native surfactant. These results suggest that the role of endogenous SP-B in host defense may be limited; however, synthetic peptides derived from SP-B may be useful in the treatment of bacterial pneumonias.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, and University of Cincinnati College of Medicine, OH 45229-3039, USA.
authors.forename: Marnie A
authors.initials: MA
authors.lastname: Ryan
authors.forename: Henry T
authors.initials: HT
authors.lastname: Akinbi
authors.forename: Alicia G
authors.initials: AG
authors.lastname: Serrano
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Gil
authors.forename: Huixing
authors.initials: H
authors.lastname: Wu
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B