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A Novel Bacterial Resistance Mechanism against Human Group IIA-Secreted Phospholipase A2: Role of Streptococcus pyogenes Sortase A.

Movert, Elin LU ; Wu, Yongzheng; Lambeau, Gérard; Touqui, Lhousseine and Areschoug, Thomas LU (2011) In Journal of Immunology 187(12). p.6437-6446
Abstract
Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA(2)-IIA. Analysis of a set of clinical isolates demonstrated that an ∼500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA(2)-IIA. We found that an S. pyogenes... (More)
Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA(2)-IIA. Analysis of a set of clinical isolates demonstrated that an ∼500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA(2)-IIA. We found that an S. pyogenes mutant lacking sortase A, a transpeptidase responsible for anchoring LPXTG proteins to the cell wall in Gram-positive bacteria, was significantly more sensitive (∼30-fold) to sPLA(2)-IIA compared with the parental strain, indicating that one or more LPXTG surface proteins protect S. pyogenes against sPLA(2)-IIA. Importantly, using transgenic mice expressing human sPLA(2)-IIA, we showed that the sortase A-mediated sPLA(2)-IIA resistance mechanism in S. pyogenes also occurs in vivo. Moreover, in this mouse model, we also showed that human sPLA(2)-IIA is important for the defense against lethal S. pyogenes infection. Thus, we demonstrated a novel mechanism by which a pathogenic bacterium can evade the bactericidal action of sPLA(2)-IIA and we showed that sPLA(2)-IIA contributes to the host defense against S. pyogenes infection. (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
Journal of Immunology
volume
187
issue
12
pages
6437 - 6446
publisher
American Association of Immunologists
external identifiers
  • wos:000298167800035
  • pmid:22075700
  • scopus:83755183819
ISSN
1550-6606
DOI
10.4049/jimmunol.1100499
language
English
LU publication?
yes
id
b8171a81-62b5-4d93-a6c7-d1d2afa69dc5 (old id 2220912)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22075700?dopt=Abstract
date added to LUP
2011-12-02 20:35:10
date last changed
2017-01-01 05:56:17
@article{b8171a81-62b5-4d93-a6c7-d1d2afa69dc5,
  abstract     = {Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA(2)-IIA. Analysis of a set of clinical isolates demonstrated that an ∼500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA(2)-IIA. We found that an S. pyogenes mutant lacking sortase A, a transpeptidase responsible for anchoring LPXTG proteins to the cell wall in Gram-positive bacteria, was significantly more sensitive (∼30-fold) to sPLA(2)-IIA compared with the parental strain, indicating that one or more LPXTG surface proteins protect S. pyogenes against sPLA(2)-IIA. Importantly, using transgenic mice expressing human sPLA(2)-IIA, we showed that the sortase A-mediated sPLA(2)-IIA resistance mechanism in S. pyogenes also occurs in vivo. Moreover, in this mouse model, we also showed that human sPLA(2)-IIA is important for the defense against lethal S. pyogenes infection. Thus, we demonstrated a novel mechanism by which a pathogenic bacterium can evade the bactericidal action of sPLA(2)-IIA and we showed that sPLA(2)-IIA contributes to the host defense against S. pyogenes infection.},
  author       = {Movert, Elin and Wu, Yongzheng and Lambeau, Gérard and Touqui, Lhousseine and Areschoug, Thomas},
  issn         = {1550-6606},
  language     = {eng},
  number       = {12},
  pages        = {6437--6446},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {A Novel Bacterial Resistance Mechanism against Human Group IIA-Secreted Phospholipase A2: Role of Streptococcus pyogenes Sortase A.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1100499},
  volume       = {187},
  year         = {2011},
}