This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01392-07v1 76/8/3399    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Johansson, L. Articles by Norrby-Teglund, A. PubMed PubMed Citation Articles by Johansson, L. Articles by Norrby-Teglund, A.

 Previous Article  |  Next Article 

Infection and Immunity, August 2008, p. 3399-3404, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01392-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans

Linda Johansson,^1, Pontus Thulin,^1, Parham Sendi,¹ Erika Hertzén,¹ Adam Linder,² Per Åkesson,² Donald E. Low,³ Birgitta Agerberth,⁴ and Anna Norrby-Teglund^1*

Center for Infectious Medicine, Karolinska Institutet, Department of Medicine—F59, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm,¹ Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm,⁴ Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden,² Department of Microbiology, Mount Sinai Hospital, and the University of Toronto, Toronto, Ontario, M5G 1x5, Canada³

Received 17 October 2007/ Returned for modification 16 December 2007/ Accepted 11 May 2008

Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococci (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial loads in the tissue even late after the onset of infection. Antimicrobial peptides are important components of the innate host defense, and cathelicidins have been shown to protect against murine necrotic skin infections caused by GAS. However, it has been demonstrated that the streptococcal cysteine protease SpeB proteolytically inactivates the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsy specimens. The results showed large amounts of LL-37, both the proform (hCAP18) and the mature peptide, in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct colocalization between the bacteria and LL-37 could be noted, and bacterial loads showed positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with large amounts of SpeB. Confocal microscopy confirmed strong colocalization of GAS, SpeB, and LL-37 at the bacterial surface. Taken together, the findings of this study provide in vivo support of the hypothesis that SpeB-mediated inactivation of LL-37 at the streptococcal surface represents a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.

Published ahead of print on 19 May 2008.

Editor: A. Camilli

L.J. and P.T. contributed equally to this work.