|
 |
|
|
| Subject Categories: Immunology | Microbiology & Pathogens |
|
| The EMBO Journal
(2006) 25, 4628–4637, doi:10.1038/sj.emboj.7601327 Published online 14 September 2006 |
|
| A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues |
|
|
| Carlos Hidalgo-Grass1, 4, Inbal Mishalian1, 4, Mary Dan-Goor1, Ilia Belotserkovsky1, Yoni Eran1, Victor Nizet2, Amnon Peled3 and Emanuel Hanski1 |
|
|
1 Institute of Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 2 Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA 3 Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel To whom correspondence should be addressed Emanuel Hanski, Faculty of medicine, Institute of Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem 91010, Israel. Tel.: +972 2 6758196; Fax: +972 2 6434170; E-mail: hanski@cc.huji.ac.il 4 These authors contributed equally to this work Received 19 May 2006; Accepted 16 August 2006; Published online 14 September 2006. |
|
|
|
| Abstract |
|
| Group A Streptococcus (GAS) causes the life-threatening infection in humans known as necrotizing fasciitis (NF). Infected subcutaneous tissues from an NF patient and mice challenged with the same GAS strain possessed high bacterial loads but a striking paucity of infiltrating polymorphonuclear leukocytes (PMNs). Impaired PMN recruitment was attributed to degradation of the chemokine IL-8 by a GAS serine peptidase. Here, we use bioinformatics approach coupled with target mutagenesis to identify this peptidase as ScpC. We show that SilCR pheromone downregulates scpC transcription via the two-component system—SilA/B. In addition, we demonstrate that in vitro, ScpC degrades the CXC chemokines: IL-8 (human), KC, and MIP-2 (both murine). Furthermore, using a murine model of human NF, we demonstrate that ScpC, but not the C5a peptidase ScpA, is an essential virulence factor. An ScpC-deficient mutant is innocuous for untreated mice but lethal for PMN-depleted mice. ScpC degrades KC and MIP-2 locally in the infected skin tissues, inhibiting PMN recruitment. In conclusion, ScpC represents a novel GAS virulence factor functioning to directly inactivate a key element of the host innate immune response. |
|
| Keywords: chemokines, group A Streptococcus , peptidase, polymorphonuclear neutrophils, virulence |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHCircumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer Nature Immunology Article (01 Oct 2001) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation Nature Medicine Article (01 Mar 2006) |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
