Streptococcous Flashcards
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
What does the superantigen do to the T cell
Binds to less variable regions (B region)
only 50 possibilities in humans
How many superantigens of S. pyogenes are there?
Many including
SmeZ
SpeG
SpeA
SpeC
SpeLM
many mobile genetic elements
maybe why strep is associated with different diseases depending on the strain
What is the mouse model of S. pyogenes?
- S. pyogenes poorly colonizes the mouse nasopharynx
- mouse MHC class II are poorly bound by bacterial superantigens
what happens in transgenic mice that express human MHC class II?
There is a 100 000 fold difference in infections due to human MHC II markers
Can strep colonize w/o certain superantigens?
In the mouse model strep has been observed to colonize much less efficiently without the superantigen SpeA
