Streptococci
Lecture 5
Medical Microbiology
SBM 2044
Streptococcus




Gram-positive
Grow in chains
Non-motile
Facultative anaerobes
 3 types of streptococci classification:
•
Early studies distinguished 3 broad groups on blood agar
• a-haemolytic
• non-haemolytic
• b-haemolytic
• Group-specific antigens (Lancefield classification) – by serological
reactivity of extracted cell wall antigens (A  U)
• Species – biochemical tests
Streptococcus pyogenes
 Natural habitat: Humans
 Strains distinguished by M serotyping
• Devised by Lancefield in 1920s, using panels of absorbed sera
to hot-HCl extracted antigen, she called “M antigen”
• M-type specific antigen was sensitive to proteases
M proteins
• > 100 distinct M types of GAS distinguished since then
- called M1, M2, M3, M4,……..etc.
 Highly versatile pathogen
• Suppurative infections
• Toxinogenic diseases
• Immunologically-mediated diseases
 GAS diseases – changing patterns
• Changes in virulence of prevailing GAS strains ?
• Changes in social conditions – less crowding?
 Reemergence of severe invasive infections
• Sporadic cases since mid-1980s – new virulent strains?
• Streptococcal toxic shock
o Some cases associated with obviously severe tissue infections
o Many others – shock following mild or unapparent infections
• Sporadic – implies predisposing factors
Group A Streptococci
Principle sites
of infection:
Pharynx
Skin
Deep-seated
tissues
Local spread (e.g.)
Invasive infections
Pharyngitis, tonsillitis,
otitis media, sinusitis.
Other tissues
pyroderma, erysipelas
Occasionally
Extensive necrosis
(necrotizing fasciitis)
Bacteraemia
or septicaemia
Streptococcal
Toxic Shock
• Puerperal fever (childbirth fever) in women – major killer in past
Streptococcus pyogenes
Tonsillitis
Follicular tonsillitis
Streptococcus pyogenes
Impetigo
Cellulitis
Erysipleas
Streptococcus pyogenes
Necrotizing fasciitis
(< 24 hours post surgery)
Streptococcus pyogenes
Scarlet fever
Group A Streptococci
• Encounter
– Carriers appear asymptomatic
– Person-to-person spread is mediated by
respiratory droplets or by direct contact to skin
• Entry
– For pyodermal infections, streptococci need to
gain entry into deeper layers of skin
– In pharyngeal infections, to prevent from
being swept away, GAS must adhere to
lipoteichoic acid (LTA), protein F and/or M
protein
M protein
• Important for cell adherence to
keratinocytes
• Prevent opsonization by
complement
– bind to fibrinogen and interferes with
the alternative pathway
– bind with host complement control
proteins and inhibit opsonins formation
• Hypervariable regions of M protein
are antigenic, but there are > 100
M protein serotypes
EM showing the M Proteins (hair-like surface
structures) of S. pyogenes
Group A Streptococci
• Spread and multiplication
– Most GAS remain localised to the site of initial
infection
– In pharynx and tonsils, may result in erythema and
exudate associated with strep throat
– Peritonsillar abscess (quinsy) or spread to adjacent
structures (mastoid and middle ear)
– Impetigo in skin
– Erysipelas and cellulitis in deeper layers of skin
– GAS may spread laterally in deep tissues, by
secreting enzymes
• necrotizing fasciitis and myositis
GAS virulence factors – Excreted products
 Cytolytic toxins
• Streptolyxin O (SLO)
Produced by all strains
• Streptolysin S (SLS)
• Both lyse wide range of cells, including PMNs
suppuration and/or necrosis
• Various subtle effects at sub-lytic concentrations
• SLO – ‘sensitive’ to O2
“Thiol-activated” toxin
• SLS – stable in O2
b-haemolysis
SLO- and SLS-defective mutants
 murine s.c. model - weight loss at 24h post infection
Sterile
~3 x 109 cfu
+ 0.5
~3 x 108 cfu
~3 x 107 cfu
~3 x 106 cfu
~3 x 105 cfu
Weight gain (grams)
0.0
- 0.5
- 1.0
- 1.5
- 2.0
- 2.5
PBS
WT
sloΔ1
sagBΔ1
sloΔ1sagBΔ1
Hyaluronic acid capsule
• Antiphagocytic structure on bacterial
surface
• Hyaluronic acid is abundant in human
connective tissue - hence GAS can
camouflaged themselves
• But capsule may interfere with the
adherence of GAS to epithelial cells
– so GAS shed the capsule during the early
stages of infection using hyaluronidase
Secreted protein
Function
Proteases
Hyaluronidase
spreading factor
Streptolysins S and O form pores in the host membranes
Deoxyribonucleases
(DNase)
Streptokinase
– bind to human protein plasminogen,
and convert this to plasmin
plasmin degrades fibrin
Damage
• GAS can evoke an intense inflammatory
responses in tissues
• Streptococcal pyrogenic exotoxins (SPE)
– SPE A, B and C cause rash, a characteristic of
scarlet fever
– SPE A and C are bacterial superantigens that activate
a large subset of T cells
• Immunologically mediated disease
(nonsuppurative sequelae)
– acute rheumatic fever (ARF)
– acute post-streptococcal glomerulonephritis
Toxic Shock
 In past – probably linked to scarlet fever
 Since mid-1980s – associated with ‘new’ highly virulent
strains - rapidly fulminating
• some cases in previously healthy young adults, no obvious
predisposing factors
 Associated with production of superantigenic toxins, but
other factors also involved
Acute rheumatic fever (ARF)
 autoimmune disease - triggered only by GAS pharyngitis
 associated with strong immune response to GAS.
• antibodies and/or T cells X-react with host antigens? (later)
 Symptoms arise > 10days + after GAS infection
• responsible GAS strain already ‘cleared’
 Symptoms may include:
• inflammation multiple sites, starting with major joints (arthritis)
• neurological disorders (Sydenhams chorea)
• rheumatic heart disease (RHD) (ca 50% cases)
- damage to heart valves, permanent scaring in survivors
Acute rheumatic fever (ARF)
 Initial attack rates low (3% in untreated pharyngitis)
 High recurrence (up to 50%) - increasing in severity
Widespread prescription of penicillin for ‘sore throats’
Remarkably, GAS have not (yet ?) developed resistance to penicillins
GAS infections - complications
Post-streptococcal acute glomerulonephritis (PSGN):
 Common, but rarely life-treating - some GAS infections
of either pharynx or skin.
 Symptoms arise some 10 days after infection
• reflect kidney dysfunction, probably involving inflammation
of glomeruli
 Pathogenesis:
• Most probably entrapment of GAS antigen-host antibody
complexes at basement membranes of glomeruli
• might also involve an ‘autoimmune’ response
Normal glomerulus
Glomerulonephritis
Mesangial cell
intrusion
Mesangial cell
Endothelial
cell, has
100 nm
pores
PMN
Basement membrane
Small complexes diffuse thro’
basement membrane into urine,
but the occasional larger complex
can’t & is normally removed by
mesangial cell
Inflammation
Too much large immune
complex entrapment ?
Example: Sequel of some
S. pyogenes infections
Treatment and Prevention
• Penicillin – 10 day oral therapy
• Erythromycin or other macrolide antibiotics
for individuals allergic to penicillin
Group B streptococci
• Streptococcus agalactiae are aerobic G+
diplococci that are β-haemolytic on blood
agar plates
– found in lower GIT and female genital tracts
– GBS is a leading cause of neonatal sepsis
and meningitis
– prevent opsonization and phagocytosis with a
polysaccharide capsule
Enterococci
• Enterococcus faecalis cause UTI, wound
infections, endocarditis, intraabdominal
abscesses and bacteremia.
–
–
–
–
–
Normal flora of GIT and GUT
resistant to bile and high salt concentrations
nosocomial infections
resistance to many antibiotics, often bacteriostatic
bacterial killing must use a combination treatment of
a β-lactam and an aminoglycoside