Necrotising Fasciitis Associated with Invasive Group A Streptococcal Infections in England and Wales

Monnickendam, Marjorie A.; McEvoy, Marion B.; Blake, Wendy A.; Gaworzewska, Ewa T.; Hallas, Gillian; Tanna, Asha; Efstratiou, A; George, R.C.

doi:10.1007/978-1-4899-1825-3_22

Cited by 9 publications

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even with prompt antibiotic treatment and surgical debridement, reported mortality rates in GAS NF and TSS are high, ranging from 20 to 60% (Davies et al , 1996; Kaul et al , 1997; Hassell et al , 2004). Although NF can be produced by GAS of various serotypes (Johnson et al , 2002; Bisno et al , 2003; Hassell et al , 2004), M1 and M3 strains have been most commonly reported (Cleary et al , 1992; Monnickendam et al , 1997; O'Brien et al , 2002; Sharkawy et al , 2002). Our prospective, population‐based study of invasive GAS infections in Israel further identified M14 strains as strongly associated with severe soft tissue infections (Moses et al , 2003).…”

Section: Introductionmentioning

confidence: 99%

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

Hidalgo-Grass

Mishalian

Dan-Goor

et al. 2006

EMBO J

137

171

View full text Add to dashboard Cite

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.

show abstract