Streptococcus pyogenes: General information
- Gram positive, thick peptidoglycan layer
- B-hemolytic, break down red blood cells when grown in blood agar
- Group A, Lancefield classification based on cell wall carbohydrate
- Forms chains that resemble a ‘string of pearls’ when viewed under the microscope
GAS: which strains are associated with disease?
High encapsulated strains
GAS: virulence
See diagram in lecture slides
GAS: general disease info
- Obligate human pathogen
- Colonizes the throat or skin
- Causes a broad spectrum of disease
GAS: Diagnosis
- Bacterial swab, and labaratory culture remain gold standard, results take 48-72hrs
- Rapid tests are now available but are less commonly used. … high false positive?
GAS: Transmission
- Human to human by direct contact
* Droplet spread from pharyngeal colonisation (sneezing, coughing)
* Touching infected skin - Contaminated fomites
* Biofilm formation may enhance survival outside the host
Rarely food source
Household crowding facilitates transmission
GAS: Carriage
The GAS carriage is poorly understood
* GAS can be carried in a benign state in the pharynx
* Carriage rates estimated to be as high as 15% in children
* Carriage rates are lower in adults, less than 5%
Carriage results in positive throat swab
* Antibiotic treatment can be prescribed for treatmnet of viral sore throat with ‘co-incidental carriage’
* GAS carriers maybe resistant to antibiotic therapy, throat swab after penicillin treatment is still positive
* UNKNOWN if GAS carriage can lead to post-infectious immune sequel (ARF and APSGN)
GAS: Penicillin
GAS is susceptible to penicillin BUT controlling disease in high burden area remains challenging.
- Not realising they need treatment
- Barriers to accessibility
- Not having full antibiotic course
- Antibiotic treatment fails in severe infections
GAS: M protein - general information
- Encoded by the emm gene
- Has a hypervariable N-terminus which provides the basis for emm typing
- Comprised of a series of repeated regions
- Conservation between GAS strains increase as you move down the protein
- C-repeat and D-repeat are highly conserved
- Extends from cell surface as coiled-coil (dimer)
- Repeat regions vary depending of emm type
- Multifunctional protein - roles in adhesion by binding fibronectin in ECM, assist in immune evasion by binding fibrinogen, factor H and immunoglobulin
GAS: Emm-typing
- Developed by the CDC in the USA
- Relies upon the use of the two highly conserved primers to amplify a large portion of the emm-gene
- The hypervariable sequence lies adjacent to one of the amplifying primer sequences, allowing for direct sequencing
GAS: emm type distribution
- emm types differ in space (geographical variation)
- Globally, emm1 is the most common emm-type in resource rich setting
- Diversity of emm-type is greater in resource poor setting
- No single dominating strain-type is associated with disease in LMIC
- emm types differ in type (temporal variation)
GAS: Emm-pattern type
Three main pattern types, A-C, D and E
GAS: Emm-pattern type - tissue tropism marker
A-C pharyngeal strains dominate in temporate climates
D pattern ‘skin’ isolates dominate in warm tropical climates
E = throat or skin
GAS: WGS
- > 200 emm-types, but this doesn’t capture all the diversity in GAS
- Strains of the same emm-type can have different phenotype driven by differences in other important virulence factors
- Emm81 outbreak in NZ aged care in winter, 2014 WGS proved useful.
- WGS not used a lot due to genome being so large and large cost
GAS: ARF symptoms
Elevated antibody titers to GAS antigens
GAS: ARF symptoms
Elevated antibody titers to GAS antigens
GAS: Pathogenesis
Poorly understood - see diagram in lecture slides
GAS: Pathogenesis
Poorly understood - see diagram in lecture slides
GAS: ARF Autoimmunity Hypothesis I
- Mimicry between M protein and human proteins found in heart tissue (myosin, collagen) - but myosin is intracellular so antibodies cannot access
- Laboratory studies only, clinical data are lacking
- Still a concern for M-protein based vaccine.
GAS: ARF Autoimmunity Hypothesis 2
