A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues.

نویسندگان

  • Carlos Hidalgo-Grass
  • Inbal Mishalian
  • Mary Dan-Goor
  • Ilia Belotserkovsky
  • Yoni Eran
  • Victor Nizet
  • Amnon Peled
  • Emanuel Hanski
چکیده

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.

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عنوان ژورنال:
  • The EMBO journal

دوره 25 19  شماره 

صفحات  -

تاریخ انتشار 2006