Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a β-hemolytic, Gram-positive bacterium that most commonly causes respiratory diseases, including pharyngitis or tonsillitis, as well as skin infections such as impetigo and cellulitis. The organism is transmitted via respiratory droplets or contact with fomites and commonly infects young children. In addition to the common clinical presentations associated with S. pyogenes, some individuals develop the postinfectious sequelae of rheumatic fever and glomerulonephritis. Due to the severity of these medical consequences, prophylactic use of antibiotics is often recommended for all patients with otherwise mild S. pyogenes infections (21). In addition to its traditional clinical manifestations, GAS can also cause serious invasive diseases such as necrotizing fasciitis, colloquially known as flesh-eating disease. First reported during the Civil War, when it was known as gangrene, necrotizing fasciitis occurs when an individual's subcutaneous fat and superficial fascia rapidly become necrotic. Although incidence data are limited, one study estimated that, worldwide, there are approximately 660,000 cases of invasive GAS disease per year, of which 97% occur in low-income populations (4). Many organisms other than GAS have been linked to necrotizing fasciitis, including Staphyloccocus aureus, Escherichica coli, and Klebsiella pneumoniae, and the disease is often caused by a polymicrobial infection. However, the best-known etiologic agent in cases of necrotizing fasciitis is usually group A streptococci (6). Although risk factors for necrotizing fasciitis include diabetes, advanced age, and immunosuppression, nearly half of all infections occur in the mid-article, approximately 24 hours after infection, during the late exponential phase and the initial stationary one. , SpeB is dramatically upregulated when tissue invasion occurs and bacteria spread ( 13 ). This upregulation is hypothesized to occur so that SpeB can cleave adhesive GAS molecules and allow bacteria to spread throughout the tissue during invasive infections ( 20 ). After diffusion of GAS at this stage, SpeB expression is again downregulated when the bacterium invades the bloodstream. GAS selects for mutations in the CovRS regulatory system, which result in reduced SpeB expression and simultaneous enhancement of the production of another virulence factor, Sda1. Sda1 helps avoid the extracellular traps of host neutrophils, allowing the bacterium to survive in the bloodstream and produce the bacteremia and sepsis characteristic of invasive GAS infections (26).