Streptococci Lecture 4

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StreptococciLecture 4

• Medical Microbiology
• SBM 2044

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Streptococcus

• Gram-positive

• Grow in chains

• Non-motile

• Facultative anaerobes

• 3 types of streptococci classification

• Early studies distinguished 3 broad groups on
  blood agar

• Group-specific antigens (Lancefield
  classification) by serological reactivity of
  extracted cell wall antigens (A ? U)
• Species biochemical tests

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• Streptococci

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• GAS diseases changing patterns

• Changes in virulence of prevailing GAS strains ?

• Changes in social conditions less crowding?

• Changes in herd immunity to prevailing virulent
  strains?

• Reemergence of severe invasive infections

• Sporadic cases since mid-1980s new virulent
  strains?

• Streptococcal toxic shock

• Some cases associated with obviously severe
  tissue infections

• Many others shock following mild or
  unapparent infections

• Sporadic implies predisposing factors

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Group A Streptococci
Principle sites of infection
Invasive infections
Local spread (e.g.)
Other tissues
Pharyngitis, tonsillitis, otitis media, sinusitis.
Pharynx
Bacteraemia or septicaemia
Skin pyroderma, erysipelas
Occasionally
Streptococcal Toxic Shock
Extensive necrosis (necrotizing fasciitis)
Deep-seated tissues

• Puerperal fever (childbirth fever) in women
  major killer in past

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Streptococcus pyogenes
Tonsillitis
Follicular tonsillitis
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Streptococcus pyogenes
Impetigo
Erysipleas
Cellulitis
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Streptococcus pyogenes
Necrotizing fasciitis
(lt 24 hours post surgery)
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Streptococcus pyogenes
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Streptococcus pyogenes
Scarlet fever
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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 lipoteichoic acid (LTA),
  protein F and M protein

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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

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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
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GAS virulence factors Excreted products

• Cytolytic toxins

• Streptolyxin O (SLO)

Produced by all strains

• Streptolysin S (SLS)

• Various subtle effects at sub-lytic
  concentrations

• SLO sensitive to O2

• SLS stable in O2

b-haemolysis
Thiol-activated toxin
(NB Salyers Whitt misleading - neither are
enzymes )
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SLO- and SLS-defective mutants

• murine s.c. model - weight loss at 24h post
  infection

Sterile
3 x 108 cfu
3 x 106 cfu
0.5
3 x 107 cfu
3 x 109 cfu
3 x 105 cfu
0.0
- 0.5
- 1.0
Weight gain (grams)
- 1.5
- 2.0
- 2.5
slo?1- sagB?1
sagB?1
WT
slo?1
PBS
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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 gt 100 M protein serotypes

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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

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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

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Diagnosis

• Impetigo a cluster of small vesicles on a pink
  base that breaks down to honey-coloured crusts
• Erysipelas a raised, bright red patch of skin
• More difficult to diagnose streptococcal
  pharyngitis
• rapid strep tests
• throat cultures (throat swab)

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Treatment and Prevention

• Penicillin 10 day oral therapy
• Erythromycin or other macrolide antibiotics for
  individuals allergic to penicillin

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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

• gt 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

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Group A Streptococci
Principle sites of infection
Invasive infections
Local spread (e.g.)
Other tissues
Pharyngitis, tonsillitis, otitis media, sinusitis.
Pharynx
Bacteraemia or septicaemia
Skin pyroderma, erysipelas
Occasionally
Streptococcal Toxic Shock
Extensive necrosis (necrotizing fasciitis)
Deep-seated tissues

• Puerperal fever (childbirth fever) in women
  major killer in past

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Streptococcus pyogenes
Tonsillitis
Follicular tonsillitis
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Streptococcus pyogenes
Impetigo
Erysipleas
Cellulitis
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Streptococcus pyogenes
Necrotizing fasciitis
(lt 24 hours post surgery)
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Streptococcus pyogenes
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Scarlet fever
Streptococcus pyogenes
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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

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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 gt 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

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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
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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

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Normal glomerulus
Glomerulonephritis
Mesangial cell
Mesangial cell intrusion
Endothelial cell, has
100 nm pores
PMN
Basement membrane
Inflammation
Too much large immune complex entrapment ?
Small complexes diffuse thro basement membrane
into urine, but the occasional larger
complex cant is normally removed by mesangial
cell
Example Sequel of some
S. pyogenes infections
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Group B streptococci

• Streptococcus agalactiae are aerobic G
  diplococci that are ß-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

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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 ß-lactam and an aminoglycoside