title: Streptolysin S and necrotising infections produced by group G streptococcus.
abstract: BACKGROUND
  We encountered three patients with severe necrotising soft tissue infections due to beta-haemolytic group G streptococcus. Due to strong clinical similarities with invasive infections produced by group A streptococcus, we investigated a potential link of shared beta-haemolytic phenotype to disease pathogenesis.
  
  
  METHODS
  Hybridisation, DNA sequencing, targeted mutagenesis, and complementation studies were used to establish the genetic basis for group G streptococcus beta-haemolytic activity. The requirement of group G streptococcus beta-haemolysin in producing necrotising infection was examined in mice.
  
  
  RESULTS
  Each patient had an underlying medical condition. beta-haemolytic group G streptococcus was the sole microbial isolate from debrided necrotic tissue. The group G streptococcus chromosome contained a homologue of the nine-gene group A streptococcus sag operon encoding the beta-haemolysin streptolysin S (SLS). Targeted mutagenesis of the putative SLS structural gene sagA in group G streptococcus eliminated beta-haemolytic activity. Mice injected subcutaneously with wild-type group A streptococcus or group G streptococcus developed an inflammatory lesion with high bacterial counts, marked neutrophil infiltration, and histopathological evidence of diffuse tissue necrosis. These changes were not found in mice injected with the isogenic group A streptococcus or group G streptococcus SLS-negative mutants.
  
  
  CONCLUSIONS
  In patients with underlying medical conditions, beta-haemolytic group G streptococcus can produce necrotising soft tissue infections resembling those produced by group A streptococcus. The beta-haemolytic phenotype of group G streptococcus is produced by the exotoxin SLS, encoded by a functional homologue of the nine-gene group A streptococcus sag operon. SLS expression contributes to the pathogenesis of streptococcal necrotising soft tissue infection.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, San Diego 92093, USA. vnizet@ucsd.edu
authors.forename: Deepali
authors.initials: D
authors.lastname: Humar
authors.forename: Vivekananda
authors.initials: V
authors.lastname: Datta
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Bast
authors.forename: Bernard
authors.initials: B
authors.lastname: Beall
authors.forename: Joyce C S
authors.initials: JC
authors.lastname: De Azavedo
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins; D003131:Combined Modality Therapy; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D003646:Debridement; D004195:Disease Models, Animal; D016521:Electrophoresis, Gel, Pulsed-Field; D019115:Fasciitis, Necrotizing / Q000382:microbiology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D016296:Mutagenesis / Q000235:genetics; D009876:Operon / Q000235:genetics; D010641:Phenotype; D011995:Recombination, Genetic / Q000235:genetics; D012703:Serotyping; D013291:Streptococcus / Q000145:classification* / Q000235:genetics* / Q000472:pathogenicity; D013297:Streptococcus pyogenes / Q000145:classification* / Q000235:genetics* / Q000472:pathogenicity; D013301:Streptolysins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014169:Transformation, Bacterial / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D013301:Streptolysins; C026050:streptolysin S