| Title: | A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues |
| Author(s): | Hidalgo-Grass C; Mishalian I; Dan-Goor M; Belotserkovsky I; Eran Y; Nizet V; Peled A; Hanski E; |
| Address: | "Institute of Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel" |
| ISSN/ISBN: | 0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking) |
| 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: | "Adhesins, Bacterial/*metabolism Animals Chemokine CXCL2 Chemokines, CXC/*metabolism Endopeptidases/*metabolism Gene Expression Regulation, Bacterial Genes, Bacterial/genetics Humans Mice Mice, Inbred BALB C Monokines/metabolism Mutation/genetics Neutrophi;" |
| Notes: | "MedlineHidalgo-Grass, Carlos Mishalian, Inbal Dan-Goor, Mary Belotserkovsky, Ilia Eran, Yoni Nizet, Victor Peled, Amnon Hanski, Emanuel eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2006/09/16 EMBO J. 2006 Oct 4; 25(19):4628-37. doi: 10.1038/sj.emboj.7601327. Epub 2006 Sep 14" |
