Streptococcus pyogenes GAS

How are streptococci classified?

Lancefield grouping

CHO antigen (cell wall carbohydrate) and hemolysis on BAP

beta hemolytic strep

• GAS: pyogenes

• GBS: agalactiae

• Bacitracin (Taxo A) sensitive: pyogens

• bacitracin resistant: agalactiae

alpha hemolytic strep

no group: pneumoniae and viridans

optichin sensitive: pneumoniae

resistant: others

gamma hemolysis

Group D

enterococci

history of GAS diseases

• started with puerperal fever, fasciitis, systemic disease

• moved to scarlet and rheumatic fever

• 1940s: fevers disappear

• late 20th century: some scarlet fever, invasive systemic, toxic shock, nosocomial, fasciitis, pneumonia

three main disease presentations of GAS and treatment

1. superficial

2. invasive (toxin-mediated)

3. sequelae

treatment: penicillin

Superficial disease

• pharyngitis/strep throat

• impetigo

• cellulitis

invasive/toxin-mediated diseases

• necrotizing streptococcal celulitis

• GAS fasciitis

• toxic shock syndrome

requirements for streptococcal TSS

1. isolation of GAS

2. clinical signs of severity

requirements for necrotizing fasciitis

1. isolation of GAS, necrosis and serious systemic disease

sequelae of GAS diseases

• Rheumatic fever: large amounts of M protein and capsule; cross-reactive with heart proteins; after strep throat

• acute glomerulonephritis: after strep throat

GAS virulence factors

• MSCRAMMs (adhesins): M proteins

• streptolysin O and S: pore-forming toxins

• enzymes: proteases, hyaluronidase, DNase, streptokinase

• hyaluronic acid capsule

• C5a peptidase

• lipoteichoic acid (LTA)

• streptococcal pyrogenic exotoxins: superantigens

GAS MSCRAMMs

• M protein: binds collagen; required for S. pyogenes virulence; antiphagocytic, LPTXG motif

• fibronectin-binding protein

• Epa: collagen binding

hyaluronic acid capsule

• discourages C3b binding (antiphagocytic)

• looks like self

C5a peptidase

• extracellular enzyme, degrades complement component C5a

• reduced migration of neutrophils to site

streptolysin O and S

SLO: oxygen sensitive hemolysin: pore-forming toxin

SLS: oxygen stable hemolysin

streptokinase

activates plasminogen: dissolve clots and extracellular matrix proteins in human cells

lipoteichoic acid

in strep cell wall

• analogous. toLPS in gram -s (endotoxin-like): septic shock

• binds to TLR2

SPEs

superantigens

• Spe A: most important

• Spe B: cysteine protease

• associated with scarlet fever, toxich shocok syndrome, necrotizing fasciitis

Why so diverse a disease spectrum?

• differences in strains

• type of toxin prpoduction

• M type

• two-component regulatory system CovRS

• many difference genes: which ones get turned on?