A Novel Bacterial Resistance Mechanism against Human Group IIA-Secreted Phospholipase A2: Role of Streptococcus pyogenes Sortase A.
(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:
https://lup.lub.lu.se/record/2220912
- author
- Movert, Elin LU ; Wu, Yongzheng ; Lambeau, Gérard ; Touqui, Lhousseine and Areschoug, Thomas LU
- organization
- publishing date
- 2011
- 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
- pmid:22075700
- 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
- 2016-04-01 13:53:46
- date last changed
- 2022-02-26 23:43:00
@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}},
doi = {{10.4049/jimmunol.1100499}},
volume = {{187}},
year = {{2011}},
}