Streptococci
General Characteristics of Streptococci
Gram positive cocci in chains or
pairs, nonmotile (except for an
occasional
flagellated
strain),
catalase-negative, form capsules
and slime layers.
Colonies are usually small, nonpigmented, and glistening.
Normal residents or agents of disease (Pyogenic pathogens) in
humans and animals; others are free-living in the environment.
Facultative anaerobes that ferment a variety of sugars, usually with
the production of lactic acid (homofermentative).
Classification Systems for Streptococci
(Lancefield grouping)
Rebecca Lancefield
(1895-1981)
Lancefield grouping based on group
specific carbohydrate antigens
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different
groups
characterized
using an alphabetic system (A, B, C ..)
Most
and
some
-hemolytic
streptococci can be typed by this
method
Classification Systems for Streptococci
Hemolysis on blood agar plates
S. pyogenes is -hemolytic (complete)
Viridans streptococci are -hemolytic (incomplete)
Enterococci are -hemolytic (no hemolysis)
S. pyogenes
showing
-hemolysis
S. pneumoniae
showing
greenish zones
typical of hemolysis.
Biochemical properties
Catalase-negative, facultative anaerobes
Major Species of Streptococcus and Related Genera
Note: Species in bold type are the most significant sources of human infection and disease.
N = none V = varies
*Urinary tract infection.
**Upper respiratory tract.
***No group C-carbohydrate identified.
Species of Streptococci
Streptococcal species
Sites of Colonization
Sites of Infection
S. pneumoniae
Oropharynx , nose
Lungs, sinuses, middle
ear, meninges
S. pyogenes
Oropharynx , rectum
Pharynx, skin, soft
tissue
S. agalacti ae
Gp. B streptococci
GU tract, Oropharynx
Neonatal
infections, CNS,
Viridans streptococci
GU tract, Oropharynx
GU tract, Cardiac valves,
bloodstream
Identification of Streptococci
Streptococcus pyogenes
Diseases caused by S. Pyogenes
Structural components of Streptococcus pyogenes
Virulence Factors of Streptococcus pyogenes
Virulence factors of S. pyogenes
Structural virulence determinants:
M protein anti-phagocytic, rapid multiplication, molecular
mimicry
Hyaluronic acid capsule antiphagocytic
Heavily encapsulated strains are very mucoid often
associated with rheumatic fever outbreaks
Only weakly immunogenic b/o similarity to connective tissue
Adhesins to host cells
Lipoteichoic acid to fibronectin on epithelial cells
Protein F1- facilitates binding to throat and skin via fibronectin
Virulence factors of S. pyogenes
Enzymes:
Streptokinase, hyaluronidase - liquefy tissue
Streptolysins (S and O) - lyse host cells
Streptolysin O is oxygen-labile
Strains lacking streptolysin S (O2-stable) are -hemolytic
under anaerobic conditions only
Exotoxins:
Pyrogenic exotoxins A-C - function as superantigens
producing a sepsis syndrome
SPE A Structurally similar to the staphylococcal superAgs
SPE B Cys protease that destroys tissue
Toxic Shock-like Sydrome (TSLS)
Caused by invasive Strep A that produce SPE
Superantigens stimulate T cells to produce large
amounts of cytokines which damage endothelial
cells causing fluid loss and rapid tissue death from
lack of oxygen
Characterized by sudden drop in blood pressure,
multi-organ failure, very high fever
Mortality rate of >30 %
Streptococcal pyrogenic exotoxins (Spe)
Produced by both the scarlet fever strains and invasive
S. pyogenes strains.
More than four serologically distinct toxins (SpeA, B, C and F).
They are superantigens (except for SpeB, which is a cysteine
protease) and may exhibit the following biological activities:
Enhances release of proinflammatory cytokines
(pyrogenicity)
causes skin rash
Spe is associated with streptococcal toxic shock syndrome or
other invasive S. pyogenes diseases.
Role of M Protein in Disease
Antigenic variations in M proteins are used to type
Group A streptococci (> 80 types)
Pharyngitis and impetigo strains differ in gene sequence
Antibody against M protein is durable and protective
but is type-specific
Strains lacking M protein are avirulent
M protein is anti-phagocytic, inhibiting (C3b)
activation of complement via the alternate pathway
M protein positive strains multiply rapidly in fresh
human blood
Epidemiology of Group A Streptococcal Pharyngitis
Humans are the natural reservoir
S. pyogenes can transiently colonize the oropharynx and skin.
Diseases are caused by recently acquired strains that can
establish an infection of the pharynx or skin.
Primarily seen in 5-15 year olds
More common in temperate/cold climates - winter
Different strains (M-protein types) are generally responsible
for pyoderma and pharyngitis
There can be relatively rapid changes in prevalent M type
strains in different areas
Asymptomatic pharyngeal carriage is relatively common
Disease caused by S. pyogenes
Suppurative
Non-Invasive
Pharyngitis (strep throat)-inflammation of the pharynx
Skin infection, Impetigo
Invasive
Scarlet fever-rash that begins on the chest and spreads
across the body
Pyoderma-confined, pus-producing lesion that usually
occurs on the face, arms, or legs
Necrotizing fasciitis-toxin production destroys tissues and
eventually muscle and fat tissue
Clinical Features of Group A Streptococcal
Pharyngitis
Difficult to distinguish from pharyngitis caused by
other pathogens
The most common cause of bacterial pharyngitis in children
Overall responsible for a small percentage of cases of
pharyngitis seen by physicians
Findings suggestive of GpA strep:
- Sore throat sudden onset, fever, headache, lymphadenitis,
tonsillar exudates
Findings not suggestive of GpA strep:
- conjunctivitis, coryza, cough, diarrhea
Suppurative sequelae - abscess, sepsis, dissemination
Nonsuppurative Sequelae of Pharyngitis
Invasive Strep A disease involve specific virulent
strains (M-1 and M-2 serotypes)
Acute Rheumatic fever:
Carditis, polyarthritis, subcutaneous nodules, chorea
Life threatening inflammatory disease that leads to damage
of heart valves muscle
Pathogenesis believed to involve molecular mimicry
Cross reactive epitopes with myosin and M protein
Glomerulonephritis:
Immunologically mediated damage perhaps resulting from
streptococcal antigens that cross react with kidney tissue
Inflammation of the glomeruli and nephrons which obstruct
blood flow through the kidneys
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Coiled-coil structure of M protein
Most variable parts of
M protein are oriented
towards outside and
provide
the
antiphagocytic effect
and
serologic
specificity.
Conserved
portions
are rooted in the cell
wall.
All four types contain
epitopes which may
stimulate the crossreactive
immune
reactions
seen
in
rheumatic fever.
Acute Rheumatic Fever (ARF)
Autoimmune state characterized by inflammation of heart
valves, joints, subcutaneous tissues and CNS
Antigenic similarities between streptococci and human
tissue antigens
Antigens stimulating Abs: most probably M protein, but
the group A carbohydrate is also a possibility
M protein epitopes involved differ from antiphagocytic
domains
Antibodies against dominant epitope of group A
carbohydrate (N-acetylglucosamine) may play role in
injury to valvular endothelium
Genetic factors are probably also important in ARF
Only a small proportion of individuals infected with Gp A
Strep
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Acute Glomerulonephritis
Caused by deposition in the glomerulus of antigen
antibody complexes with complement activation and
consequent destruction of glomerular membrane,
allowing blood and proteins to leak into urine
Type II hypersensitivity reaction
M proteins of some nephritogenic strains share
antigenic determinants with glomeruli
Streptokinase also been implicated both through
molecular mimicry and through its plasminogen
activation capacity
Pathogenesis of Streptococcal Pharyngitis
Bacteria are spread by droplets or nasal secretions.
Crowding increases the risk of spread
Strains rich in both M protein and hyaluronate
appear to be more easily transmitted
Streptococci adhere to epithelial cells using adhesins
- protein F1 and lipoteichoic acid
Susceptibility to infection is determined by the
presence of type-specific antibody to M protein
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Diagnosis
As noted clinical criteria for streptococcal
pharyngitis of limited value
Culture remains the gold standard
Rapid streptococcal antigen detection kits
based on carbohydrate recognition are highly
specific
Treatment/Prevention of S. pyogenes
Infection
The species remains exquisitely sensitive to penicillin
The use of antibiotics that are protein synthesis
inhibitors (e.g. clindamycin) that inhibit protein
synthesis may improve outcome
Soft tissue infections often require surgical
debridement
Intravenous immunoglobulin may also have a
beneficial role
Prophylactic antibiotics
Vaccines - under investigation
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