Innate antimicrobial peptide protects the skin from invasive bacterial infection

Victor Nizet, Takaaki Ohtake, Xavier Lauth, Janet Trowbridge, Jennifer Rudisill, Robert A. Dorschner, Vasumati Pestonjamasp, Joseph Piraino, Kenneth Huttner and Richard L. Gallo ()
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Victor Nizet: University of California
Takaaki Ohtake: University of California
Xavier Lauth: University of California
Janet Trowbridge: University of California
Jennifer Rudisill: University of California
Robert A. Dorschner: University of California
Vasumati Pestonjamasp: University of California
Joseph Piraino: Massachusetts General Hospital
Kenneth Huttner: Massachusetts General Hospital
Richard L. Gallo: University of California

Nature, 2001, vol. 414, issue 6862, 454-457

Abstract: Abstract In mammals, several gene families encode peptides with antibacterial activity, such as the β-defensins and cathelicidins1,2,3. 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’4,5. The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated6,7,8 and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro9,10,11,12,13. 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 family14. The mature human (LL-37)15 and mouse (CRAMP)16 peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar α-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).

Date: 2001
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DOI: 10.1038/35106587

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