Describe Streptococci
- Gram-positive, coccus shaped,
- aerotolerant anaerobes, grow in chains
- ”Streptos” – Greek for bent or twisted
- non-motile, non-endospore forming
- Initially classified by their pattern of hemolysis on blood agar
what is the difference between alpha-hemolytic
beta-hemolytic and gamma-hemolytic streptococci how are they classified?
“Lancefield Classification”
• classified on the basis of surface carbohydrate antigens
Alpha
- S. pneumoniae (pneumococcus)
- viridans group including:
- S. viridans - endocarditis (important for causing infection but non pathogenic)
- S. mutans – tooth decay
- S. thermophilus – dairy food (not infectious)
Beta (disease causing)
- S. pyogenes (Group A Streptococcus)
- S. agalactiae (Group B Streptococcus)
- S. equi (Group C Streptococcus)
Gamma
- Enterococcus species (Group D Streptococcus)
- Lactococcus lactis (Group N Streptococcus)
describe S. pyogenes
Common human specific pathogen
extracellular pthogen
“pyo” = pus
5-15% asymptomatic arriage
What does S. pyogenes cause?
historically a major cause of mortality due to
- scarlet fever
- pueperal sepsis
- wound infections in soldiers
Today a common cause of
- Pharyngitis
- impetigo
- sever invasive stretococcal disease
- streptococcal toxic shock syndrome (flesh eating disease)
- important cause of post infection sequelae including acute rheumatic fever (Get infection, infection goes away and disease appears)
How dangerous are S. pyogenes virulence factors?
Arsenal of key virulence factors
a mastero at hiding from immune system
armed to cause severe damage
What does the M protein do in S. pyogenes?
an anti-phagocytic cell surface expressed protein
– binds “Factor H” of the complement system
– Factor H is a complement regulatory protein that
protects self cells from C3b deposition
– >100 M protein serotypes
– hypervariable(changing) N-terminus – basis for M protein serotypes
• e.g. M1, M3 typically cause pharyngitis and
invasive disease
• e.g. M18 typically cause acute rheumatic fever
How can humans combat M proteins?
antibodies to a particular M protein serotype will opsonize and kill these bacteria
What are the 2 hemolysins(targets red cells and other cells) S. pyogenes makes?
Streptolysins (O and S)
– streptolysin S produces β-hemolysis
– streptolysin O is “O2-sensitive” – can be seen under anaerobic conditions
What is a hyaluronic acid capsule in S. pygoenes
- a polysaccharide
- hyaluronic acid is a major component of host tissues – bacteria “look like self”
- can also block opsonization through
- C3b (typical of other capsules)
What are streptococcal pyrogenic exotoxins and what do they do? (Spe’s)
- Secreted exotoxins
- superantigens
- all S. pyogenes strains make between 4 and 8 different superantigens
- function as potent activators of T cells resulting in a cytokine storm disease known as the toxic shock syndrome
- Not emetic like the staphylococcal enterotoxins
What does the DNAse (Streptodornase) do?
- Lets bacteria escape from NET
- enzyme that degrades DNA
- secreted exotoxin
- targets NETs (Neutrophil extracellular traps)
How do NETs form?
- Activation leads to formation of reactive O2 species
- Loss of nuclear structure – spilling into cytoplasm
- DNA mixes with granules
- Loss of cell membrane integrity and release of NETs
what deomgraphic is pharyngitis most common in?
school aged children and teenagers
What are symtoms of pharyngitis
- fever and severe sore throat
- typically absence of cough
- swollen cervical lymph nodes
- tonsillar exudate (pus)
- skin rash
How do you determine if strep throat (pharyngitis) is viral or bacterial?
diagnosed by a rapid strep test
- positive test = strep throat = antibiotics
- negative test = throat culture
treated with antibiotics
- penicillins (no documented resistance!!!!)
- erythromycin (resistant strain exist)
- erythromycin only if allergic to penicillin
untreated pharyngitis can lead to a number of complications including acute rheumatic fever
Describe Impetigo
- most common among children
- also caused by S. aureus
- a superficial skin infection
- red sores that forms crusts, normally on the face
- highly contagious through direct contact (especially children)
Describe the Scarlet fever
“scarlatina”
rash that develops typically during strep throat
5-15 years of age
high fever, “strawberry tongue”
rash – small red bumps
- normally on the chest and stomach
- can look like a sunburn
- rough sandpaper
- lasts 2-7 days
toxin mediated - caused by the “scarlet fever toxins” (superantigens)
- same toxins as streptococcal pyrogenic exotoxins
Describe Acute Rheumatic fever
a “post infection” sequelae
occurs 2-3 weeks after infection (e.g. strep throat or scarlet fever)
typically occurs in children 5-15 years of age
caused by antibody cross reactivity with the M protein
a form of autoimmunity
rare in developed counties since 1960s but endemic in many developing countries
What can Acute rheumatic fever cause
can cause painful swollen joints
heart tissue targeted = damages heart valves
acute rheumatic fever = the initial flare up
rheumatic heart disease = when the valves are damaged
can be permanent
can lead to congestive heart failure – heart can’t pump enough blood
patients are at increased risk for infective endocarditis by other pathogens
Is group A strep a top 10 killer for individual pathogens?
Yes it is # 9 on the list of global mortality from individual pathogens
Describe invasive streptococcal disease
- rare in developed countries but very serious
- • “invasive streptococcal disease” is defined as isolation of S. pyogenes from a normally sterile site
- • blood isolation = bacteremia
- • if soft tissue involved = necrotizing fasciitis
- • if muscle involved = necrotizing myositis
- The disease: Invasive streptococcal disease
- • streptococcal toxic shock syndrome = flesh-eating disease
Describe events of Day 0 - 4 of invasive streptococcal disease
Trauma (day zero)
- Discomfort in the general region of the
- Pain that is out of proportion with the
severity of the injury (day one)
- Influenza-like symptoms
- Swelling or sunburn-type redness in the general region of the injured area (day two)
- Worsening of the condition and less frequent urination
- Large, boil-like blisters (bullae) containing pus (day 2-3)
- Haemorrhage from the bullae
- Gangrene (day four)
What is treatment for Invasive Streptococcal disease
- Antibiotics
- Supportive therapy
- Debridement/amputation - take tissue out
- Intravenous immunoglobulin (IVIG) - pooled antibodies
- neutralize superantigen activity
- opsonization of S. pyogenes
What are risk factors for invasive streptococcal disease?
Tissue injury (penetrating and nonpenetrating)
Prior use of nonsteroidal antiinflammatory agents
Chicken pox in children (58-fold increased risk)
- should get vaccine
Postpartum
Lack of immunity to superantigens and M protein
MHC class II haplotypes (ie. superantigen receptors)
- Some bind better to superantigen making the disease mroe infections
