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

Johansson, Linda; Thulin, Pontus; Sendi, Parham; Hertzén, Erika; Linder, Adam LU ; Åkesson, Per LU ; Low, Donald E; Agerberth, Birgitta and Norrby-Teglund, Anna (2008) In Infection and Immunity 76(8). p.3399-3404
Abstract
Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate 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 biopsies.... (More)
Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate 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 biopsies. The results showed high amounts of LL-37, both the proform (hCAP18) and the mature peptide, present in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct co-localization between the bacteria and LL-37 could be noted, and bacterial load showed a positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with high amounts of SpeB. Confocal microscopy confirmed a strong co-localization of GAS, SpeB and LL-37 at the bacterial surface. Taken together the findings of this study provides in vivo support that SpeB-mediated inactivation of LL-37 at the streptococcal surface represent a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
76
issue
8
pages
3399 - 3404
publisher
American Society for Microbiology
external identifiers
  • wos:000258480900004
  • pmid:18490458
  • scopus:48849117760
ISSN
1098-5522
DOI
10.1128/IAI.01392-07
language
English
LU publication?
yes
id
4d1d3ed7-9159-4f65-a659-cb4eb5379e59 (old id 1153954)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18490458?dopt=Abstract
date added to LUP
2008-06-04 10:50:22
date last changed
2017-04-09 03:32:48
@article{4d1d3ed7-9159-4f65-a659-cb4eb5379e59,
  abstract     = {Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate 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 biopsies. The results showed high amounts of LL-37, both the proform (hCAP18) and the mature peptide, present in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct co-localization between the bacteria and LL-37 could be noted, and bacterial load showed a positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with high amounts of SpeB. Confocal microscopy confirmed a strong co-localization of GAS, SpeB and LL-37 at the bacterial surface. Taken together the findings of this study provides in vivo support that SpeB-mediated inactivation of LL-37 at the streptococcal surface represent a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.},
  author       = {Johansson, Linda and Thulin, Pontus and Sendi, Parham and Hertzén, Erika and Linder, Adam and Åkesson, Per and Low, Donald E and Agerberth, Birgitta and Norrby-Teglund, Anna},
  issn         = {1098-5522},
  language     = {eng},
  number       = {8},
  pages        = {3399--3404},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans},
  url          = {http://dx.doi.org/10.1128/IAI.01392-07},
  volume       = {76},
  year         = {2008},
}