(B) Lecture 19: Streptococcus pyogenes Flashcards
Streptococci
- gram-POSITIVE
- coccus shaped
- grows in chains (bent or twisted)
- hemolysis on blood agar
Alpha hemolysis
Streptococci
- green colour
- PARTIAL hemolysis of blood
- S. pneumoniae
Viridans group includes:
- S. viridans: endocarditis (invades blood + causes heart problems)
- S. mutans: tooth decay
- S. thermophilus: dairy foods
Beta hemolysis
Streptococci
- COMPLETELY lysing hemoglobin
- S. pyogenes (Group A streprococcus)
- S. agalactiae (Group B streptococcus)
Gamma hemolysis
Streptococci
NO hemolysis
- Enterococcus species (Group D streptococcus)
- Lactococcus lactis (Group N streptocous) - another dairy organism
Lancefield classification
classified on basis of surface carbohydrate antigens
Streptococcus pyogenes
- human-specific pathogen
- 5-15% asymptomatic carriage
- extracellular pathogen (pyo = pus)
- major cause of scarlet fever, puerperal sepsis and wound infections
- today a common cause of pharyngitis (strep throat) + impetigo
- also causes severe invasive streptococcal disease and streptococcal toxic shock syndrome (“flesh-eating”)
- important cause of “post infection sequelae” like acute rheumatic fever
S. pyogenes virulence factors
- M protein
- Hyaluronic acid capsule
- Hemolysins
- Superantigens
M protein
S. pyogenes
- main hallmark
- PROTECTS BACTERIA FROM COMPLEMENT SYSTEM
- anti-phagocytic cell surface protein
- binds C4 binding protein of host = protects bacteria from complement
- however, if you have antibodies to a specific M protein serotype, you will opsonize + kill the bacteria
Hyaluronic acid capsule
S. pyogenes
- polysaccharide
- hyaluronic acid is major component of host tissue - bacteria looks like self
- can’t make a vaccine against it b/c it would target self cells
- can also block opsonization through C3b
Hemolysins
S. pyogenes makes 2 hemolysisn
Streptolysins: O and S
- streptolysin S produces beta hemolysis
- streptolysin O is O2 sensitive
Streptolysin S
produces beta hemolysis
makes capsule and clears around itself using hemolytic toxin
Superantigens
- secreted exotoxins
- Streptococcal Pyrogenic Exotoxins (Spe’s) = induces fevers
- act as potent T cell activators
- can result in cytokine storm and lead to toxic shock syndrome
Pharyngitis
- most common in school-aged children and teenagers
- fevers and severe sore throat
- absence of cough
- swollen cervical lymph nodes
- tonsillar exudate (pus)
Diagnosis and treatment of pharyngitis
Diagnosed by rapid strep test
- looking for group A carb antigen
- positive test = strep throat –> antibiotics
- negative test –> throat culture
Treated with antibiotics
- beta-lactams (no documented resistance) – ex. amoxicillin
- erythromycin (resistant strain) - for ppl allergic to penicillin
Untreated pharyngitis = acute rheumatic fever
Impetigo
- common among children
- caused by Staphylococcus aureus
- superficial skin infection
- red sores that form crusts, usually on face
- highly contagious thru direct contact
Scarlet Fever
- rash develops during strep throat
- high fever, strawberry/red tongue
- rash - small red bumps (rough sandpaper feel)
- toxin-mediated caused by scarlet fever toxins (same toxins as S. pyogenic exotoxins)
Rheumatic Fever
- “post-infection” sequelae
- caused by AUTOIMMUNE response
- 2-3 weeks after infection
- autoimmunity caused by antibody cross-reactivity w/ M protein
- acute rheumatic fever = initial inflammation can cause swollen joints
- rheumatic heart disease = damaged heart valves
Rare in high-income countries but endemic in low resource settings
Invasive streptococcal disease
Invasive: able to isolate organism from usually sterile site
- rare in developed countries
- blood isolation –> bacteremia
Flesh eating disease
- soft tissue involved = necrotizing fasciitis
- muscle involved = necrotizing myositis
- streptococcal toxic shock syndrome
Risk factors for invasive streptococcal disease
- tissue injury (bruise or penetrating)
- chicken pox in kids (lesions allow entry)
- postpartum
- lack of immunity to superantigens and M protein
- MHC class II haplotypes (superantigen receptors) - wrong set of MHC class II and superantigen binding well = more likely to develop
Treatment of invasive streptococcal disease
- antibiotics (protein synthesis inhibitors)
- debridement/amputation
- IVIG (neutralize superantigen activity + opsonizes S. pyogenes)
Superantigen-mediated T cell activation
Superantigen is not processed by APC like conventional binding
Superantigen wedges receptor apart
- T cell can’t recognize antigen and becomes independent of antigen
- superantigen causes activation of huge number of T cells = cytokine storm
- superantigen binds directly to MHC class II and not APC
Mouse model of S. pyogenes
S. pyogenes is human-specific pathogen
Superantigens do NOT bind well to mouse MHC class II
Without SpeA = barely infect
Without all superantigens = bacteria can’t infect
Induced rheumatic heart disease
- Mitral valve is mostly targeted w/ rheumatic heart disease
- Left ventricle pumps most blood
Control = no infection
WT (fully-loaded pathogen) = heart impaired
- drop in EF and raise in E/A ratio
- LV can’t push out as much blood
No M protein = no infection
Ejection fraction
how much blood heart can pump out every LV contracts
Important contributors to S. pyogenes
- MHC Class II
- Superantigens act as colonization factors (should be considered for vaccines)
- M protein is an important virulence factor for experimental rheumatic heart disease
Important virulence factors of Rheumatic heart disease
M protein is an important virulence factor
M protein knocked out = no reduction in EF and no increase in E/A ratio
- nor as effective at infection
