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Staphylococcal Proteases Aid in Evasion of the Human Complement System.

Jusko, Monika LU ; Potempa, Jan; Kantyka, Tomasz; Bielecka, Ewa LU ; Miller, Halie K; Kalinska, Magdalena; Dubin, Grzegorz; Garred, Peter; Shaw, Lindsey N and Blom, Anna LU (2014) In Journal of Innate Immunity 6(1). p.31-46
Abstract
Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of... (More)
Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of human serum with the cysteine proteases staphopain A and staphopain B, the serine protease V8 and the metalloproteinase Aur resulted in a drastic decrease in the hemolytic activity of serum, whereas two staphylococcal serine proteases D and E, had no effect. These four proteases were found to inhibit all pathways of complement due to the efficient degradation of several crucial components. Furthermore, S. aureus mutants lacking proteolytic enzymes were found to be more efficiently killed in human blood. Taken together, the major proteases of S. aureus appear to be important for pathogen-mediated evasion of the human complement system. © 2013 S. Karger AG, Basel. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Innate Immunity
volume
6
issue
1
pages
31 - 46
publisher
Karger
external identifiers
  • wos:000330151600005
  • pmid:23838186
  • scopus:84893682791
ISSN
1662-811X
DOI
10.1159/000351458
language
English
LU publication?
yes
id
da18d374-df7f-4f84-9227-9ea4dd6cdc2e (old id 3956046)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23838186?dopt=Abstract
date added to LUP
2013-08-02 11:35:56
date last changed
2017-10-01 03:16:43
@article{da18d374-df7f-4f84-9227-9ea4dd6cdc2e,
  abstract     = {Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of human serum with the cysteine proteases staphopain A and staphopain B, the serine protease V8 and the metalloproteinase Aur resulted in a drastic decrease in the hemolytic activity of serum, whereas two staphylococcal serine proteases D and E, had no effect. These four proteases were found to inhibit all pathways of complement due to the efficient degradation of several crucial components. Furthermore, S. aureus mutants lacking proteolytic enzymes were found to be more efficiently killed in human blood. Taken together, the major proteases of S. aureus appear to be important for pathogen-mediated evasion of the human complement system. © 2013 S. Karger AG, Basel.},
  author       = {Jusko, Monika and Potempa, Jan and Kantyka, Tomasz and Bielecka, Ewa and Miller, Halie K and Kalinska, Magdalena and Dubin, Grzegorz and Garred, Peter and Shaw, Lindsey N and Blom, Anna},
  issn         = {1662-811X},
  language     = {eng},
  number       = {1},
  pages        = {31--46},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Staphylococcal Proteases Aid in Evasion of the Human Complement System.},
  url          = {http://dx.doi.org/10.1159/000351458},
  volume       = {6},
  year         = {2014},
}