Streptolysin S and necrotising infections produced by group G streptococcus

D Humar, V Datta, DJ Bast, B Beall, JCS De Azavedo… - The Lancet, 2002 - thelancet.com
D Humar, V Datta, DJ Bast, B Beall, JCS De Azavedo, V Nizet
The Lancet, 2002thelancet.com
Background We encountered three patients with severe necrotising soft tissue infections due
to β-haemolytic group G streptococcus. Due to strong clinical similarities with invasive
infections produced by group A streptococcus, we investigated a potential link of shared β-
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 β-haemolytic activity. The requirement of group G …
Background
We encountered three patients with severe necrotising soft tissue infections due to β-haemolytic group G streptococcus. Due to strong clinical similarities with invasive infections produced by group A streptococcus, we investigated a potential link of shared β-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 β-haemolytic activity. The requirement of group G streptococcus β-haemolysin in producing necrotising infection was examined in mice.
Findings
Each patient had an underlying medical condition.β-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 β-haemolysin streptolysin S (SLS). Targeted mutagenesis of the putative SLS structural gene sagA in group G streptococcus eliminated β-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 Gstreptococcus SLS-negative mutants.
Interpretation
In patients with underlying medical conditions, β-haemolytic group G streptococcus can produce necrotising soft tissue infections resembling those produced by group A streptococcus. The β-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.
thelancet.com