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  • 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,a, Inbal Mishalian1,a, 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

Correspondence to:

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

aThese authors contributed equally to this work

Received 19 May 2006; Accepted 16 August 2006

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