title: Innate antimicrobial peptide protects the skin from invasive bacterial infection.
abstract: In mammals, several gene families encode peptides with antibacterial activity, such as the beta-defensins and cathelicidins. These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as 'natural antibiotics'. The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro. To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family. The mature human (LL-37) and mouse (CRAMP) peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar alpha-helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS).
authors.affiliation: Department of Pediatrics, University of California, San Diego, California 92161, USA.
authors.forename: V
authors.initials: V
authors.lastname: Nizet
authors.forename: T
authors.initials: T
authors.lastname: Ohtake
authors.forename: X
authors.initials: X
authors.lastname: Lauth
authors.forename: J
authors.initials: J
authors.lastname: Trowbridge
authors.forename: J
authors.initials: J
authors.lastname: Rudisill
authors.forename: R A
authors.initials: RA
authors.lastname: Dorschner
authors.forename: V
authors.initials: V
authors.lastname: Pestonjamasp
authors.forename: J
authors.initials: J
authors.lastname: Piraino
authors.forename: K
authors.initials: K
authors.lastname: Huttner
authors.forename: R L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins; D017192:Skin Diseases, Bacterial / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D011506:Proteins; D011993:Recombinant Fusion Proteins