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MEDICAL MICROBIOLOGY I

Lesson 9
Streptococcus and Diseases

Streptococcus
The genus Streptococcus is a diverse collection
of Gram positive cocci typically arranged in
pairs or chains
Most species are facultative anaerobes, and
some grow only in an atmosphere enhanced
with carbon dioxide (capnophilic growth)
Their nutrient requirements are complex,
necessitating the use of blood- or serumenriched media for isolation

Streptococcus

Streptococcus
Carbohydrates are fermented, resulting in the
production of lactic acid
Catalase negative
Most -haemolytic strains and some haemolytic and non-haemolytic strains
possess group-specific antigens, most of which
are cell wall carbohydrates

Streptococcus
These antigens can be readily detected by
immunologic assays and have been useful for
the rapid identification of some streptococcal
pathogens
Most -haemolytic

and non-haemolytic
streptococci do not possess the group-specific
cell wall antigens
These organisms must be identified from their
physiologic properties

Streptococcus pyogenes
2 species of streptococci are classified in group
A:
S. pyogenes (flesh-eating bacteria)
S. angionosus

S. pyogenes is the most common pathogen


S. pyogenes is an important cause of a variety of
suppurative and non-suppurative diseases
They are the most common cause of bacterial
pharyngitis, these organisms have become
notorious because they can cause dramatic, lifethreatening diseases

Streptococcus pyogenes

Streptococcus pyogenes
1. Physiology and Structure
0.5 - 1.0 m, spherical cocci that form short
chains in clinical specimens and longer chains
when grown in liquid media
Growth is optimal on enriched blood agar
media but it is inhibited if the medium contain
high concentration of glucose
After 24 hrs incubation, 1 - 2 mm white
colonies with large zones of -haemolysis are
observed

Streptococcus pyogenes
Encapsulated strains may appear mucoid on
freshly prepared media but wrinkled on dry
media
Non-encapsulated colonies are smaller and
glossy
Cell wall: peptidoglycan (gram positive); within
the cell wall are group-specific and typespecific antigens

Streptococcus pyogenes
2. Group-Specific Carbohydrates
The group specific carbohydrate, which
constituents approximately 10% of the dry
weight of the cell, is a dimer of Nacetylglucosamine and rhamnose
This antigen is used to classify group A
streptococci and distinguish them from other
streptococcal groups

Streptococcus pyogenes
3. Type-Specific Proteins
The M protein is a major type-specific protein
associated with virulent streptococci
M proteins are subdivided into class I and class
II molecules
The type I M proteins have the constant (C)
exposed, whereas antibodies do not develop
against the C region of class II M proteins

Streptococcus pyogenes

Streptococcus pyogenes
This appears to be important for patients who
develop rheumatic fever, because their disease
is mediated by strains with the class I M
proteins
A secondary type-specific protein that is useful
epidemiologic marker for bacterial strains that
fail to express the M protein is the t protein
(trypsin-resistant)

Streptococcus pyogenes
4. Other Surface Components
M-like proteins, lipoteichoic acid and F-protein
The M-like proteins are encoded by a complex
of more than 20 genes that comprises the
emm gene superfamily
These genes are responsible for M proteins, Mlike proteins, and other immunoglobulinbinding proteins

Streptococcus pyogenes
Lipoteichoic acid and F protein facilitate binding
of host cells by complexing with fibronectin,
which is present on the host cell surface
Capsule-composed of hyaluronic acid
containing repeating molecules of glucuronic
acid and N-acetylglucosamine; prevent
phagocytosis by providing physical barrier
between the opsonic complement proteins
bound to the bacterial surface and phagocytic
cells

Streptococcus pyogenes
5. Pathogenesis and Immunity
The virulence of group A streptococci is
determined by the ability of the bacteria to
adhere to the surface of host cells, invade into
the epithelial cells, avoid opsonisation and
phagocytosis, and produce a variety of toxins
and enzymes
More than 10 different bacterial antigens have
been demonstrated to mediate adherence to
host cells, with lipoteichoic acid, M proteins,
and F protein the most important, as well as
other antigen

Streptococcus pyogenes
The internalisation is believed to be important
for maintenance of persistent infections (e.g.
recurrent streptococcal pharyngitis) as well as
invasion into deep tissues
Streptococcus pyogenes has multiple
mechanisms for avoiding opsonisation and
phagocytosis
M-related proteins interfere with phagocytosis,
peptidase block chemotaxis of neutrophils and
mononuclear phagocytes

Streptococcus pyogenes
6. Pyrogenic exotoxins
The streptococcal pyrogenic exotoxins (Spes),
originally called erythrogenic toxins are
produced by lysogenic strains of streptococci
and are similar to the toxin produced in
Corynebacterium diphtheriae
3 immunologically distinct heat-labile toxins
(SpeA, SpeB and SpeC) have been described in
S. pyogenes and in rare strains of groups C and
G of streptococci

Streptococcus pyogenes
The toxins act as superantigens, interacting
with both macrophages and helper T cells with
the release of interleukin-1 (IL-1), IL-2, and IL6, tumour necrosis factor- (TNF- ) and TNK and interferon-
These cytokines mediate a variety of important
effects, including the shock and the organ
failure seen characteristically inpatients with
streptococcal toxic shock syndrome

Streptococcus pyogenes
7. Streptolysin S and O
Streptolysin S is an oxygen-stable, nonimmunogenic, cell-bound haemolysin that can
lyse erythrocytes, leukocytes and platelets
Streptolysin S is produced in the presence of
serum (serum dependence) and is responsible
for the characteristic -haemolysis seen on
blood agar media

Streptococcus pyogenes
Streptolysin O is oxygen-labile haemolysin
capable of lysing erythrocytes, leukocytes,
platelets, and cultured cells
Antibodies are readily formed against
streptolysin O, a feature differentiating it from
streptolysin S, and are useful for documenting
recent group A infection (ASO test)
Streptolysin O is irreversibly inhibited by
cholesterol in skin lipids

Streptococcus pyogenes
8. Streptokinases
2 forms: streptokinase A and B
These enzymes can lyse blood clots and may
be responsible for the rapid spread of
Streptococcus pyogenes in infected tissues
Anti-streptokinase antibodies are also a useful
marker for infection

Streptococcus pyogenes
9. Deoxyribonucleases
4 immunologically distinct DNases: A to D
These enzymes are not cytolytic but can
depolymerise free DNA present in pus
This process reduces the viscosity of the
abscess material and facilitates spread of the
organisms
Antibodies developed against DNase B are an
important marker of cutaneous Streptococcus
pyogenes infections

Streptococcus pyogenes
10.C5a Peptidase
Complement component C5a mediates
inflammation by recruiting and activating
phagocytic cells
C5a peptidase disrupts this process by
degrading C5a

Clinical Diseases
1. Pharyngitis
This develops 2 - 4 days after exposure to the
pathogen, with an abrupt onset of sore throat,
fever, malaise, and headache
The posterior pharynx can appear
erythematous with an exudate, and cervical
lymphadenopathy can be prominent
50% of patients with strep throat have
pharyngeal or tonsilar exudates

Pharyngitis Strep Throat

Clinical Diseases
2. Scarlet Fever
A complication of streptococcal pharyngitis
that occurs when the infecting strain is
lyosogenised by a temperate bacteriophage
that stimulate the production of a pyrogenic
exotoxin
Within 1 to 2 days after the initial clinical
symptoms of pharyngitis develop, a diffuse
erythematous rash initially appears on the
upper chest and then spreads to the
extremities

Scarlet Fever

Clinical Diseases
The area around the mouth is generally
spared, as are the palms and sole
A yellowish white coating initially covers the
tongue and is later shed, revealing a red, raw
surface beneath (strawberry tongue)
The rash disappears over the next 5 - 7 days
and is followed by desquamation

Clinical Diseases
3. Pyoderma (Impetigo)
A confined, purulent (pyo) infection of the
skin (derma) that primarily affects exposed
areas (e.g. face, arms, legs)
Through direct contact
Vesicles develop and then become pustules
(pus-filled vesicles), which then rupture and
crust over
The regional lymph nodes can become
enlarged, but systemic signs of infection (e.g.
fever, sepsis) are uncommon

Pyoderma

Clinical Diseases
Pyoderma is seen primarily in young children
(2 - 5 years old) with poor personal hygiene
and occurs primarily in warm, moist summer
months
The strains of streptococci that cause skin
infections are different from those that cause
pharyngitis, although pyoderma serotypes can
colonise the pharynx and establish a persistent
carriage state

Clinical Diseases
4. Erysipelas
An acute infection of the skin
Patients experience local pain and
inflammation (erythema, warmth), lymph
node enlargement, and systemic signs (chill,
fever, leukocytosis)
The involved skin area is typically raise and
distinctly differentiated from the uninvolved
skin

Erysipelas

Clinical Diseases
5. Cellulitis
Typically involves the skin and deeper
subcutaneous tissue, and the distinction
between the infected and non-infected skin is
not clear
Precise identification of the offending
organism is necessary because many different
microbes can cause cellulitis

Cellulitis

Clinical Diseases
6. Necrotising Fasciitis
An infection that occurs deep in the
subcutaneous tissue, spreads along the fascial
planes and is characterised by an extensive
destruction of muscle and fat
The organism is introduced into the tissue
through a break in the skin
Initially there is evidence of cellulitis, after
which bullae form and gangrene, and other
systemic symptoms develop

Necrotising Fasciitis

Clinical Diseases
Systemic toxicity, multi-organ failure and death
(>50%) are the hallmarks of this disease
Fasciitis must be treated aggressively with the
surgical debridement of non-viable tissue

Clinical Diseases
7. Streptococcal Toxic Shock Syndrome
Most patients initially experience soft tissue
inflammation at the site of the infection and pain
as well as non-specific symptoms, such as fever,
chills, malaise, nausea, vomiting and diarrhoea
The pain intensifies as the disease progresses to
shock and organ failure
Patients with streptococcal disease are
bacteremic, and most have necrotising fasciitis
Susceptible: HIV, diabetic, cancer, heart or
pulmonary disease and varicella-zoster viral
infection patients

Clinical Diseases
8. Other Disease
I. Suppurative

Puerperal sepsis
Lymphangitis
Pneumonia

II. Non-suppurative

Rheumatic fever
Acute glomerulonephritis

Lymphangitis

Laboratory Diagnosis
Microscopic: Gram stain
Antigen detection: immunologic test using
antibodies that react with the group-specific
carbohydrate in the bacterial cell wall, e.g.
enzyme immunoassay (EIA)
Culture: haemolysis on blood agar media
Identification: bacitracin
Antibody detection: ASO test, anti-DNase test

Bacitracin Test

Streptococcus agalactiae
Streptococcus agalactiae is the only species
that carries the group B antigen
This organism was initially recognised as a
cause of puerperal sepsis, later known as an
important cause of septicaemia, pneumonia,
and meningitis in newborn children, as well as
a cause of serious disease in adults

Streptococcus agalactiae

Streptococcus agalactiae
1. Physiology and Structure
Gram positive cocci (0.6 - 1.2 m) that form
short chains in clinical specimen and longer
chains in culture
They grow well in nutritionally enriched media
and in contrast with a narrow zone of haemolysis
Some strains (1-2%) are non-haemolytic,
although their prevalence may be
underestimated because non-haemolytic strains
are not screened for the group B antigen

Streptococcus agalactiae
Strains of S. agalactiae can be subdivided on
the basis of the 3 serologic markers:
The B antigen or group-specific cell wall
polysaccharide antigen (composed of
rhamnose, N-acetylglucosamine, and galactose)
Type-specific capsular polysaccharides (Ia, Ib, II
to VIII)
The surface protein, C protein

Streptococcus agalactiae
2. Pathogenesis and Immunity
Antibodies developed against the type-specific
capsular antigens of group B streptococci are
protective, a factor that partly explains the
predilection of this organism for neonates
Genital colonisation with group B streptococci
has been associated with increased risk of
premature delivery
Group B streptococci produce several enzymes,
including DNases, hyaluronidase, neuraminidase,
protease, hippurase, and haemolysins

Clinical Diseases
Early-Onset Neonatal Disease
Bacteremia, pneumonia, or meningitis

Late-Onset Neonatal Disease


Acquired from an exogenous source (e.g. mother, another
infant). Bacteremia with meningitis

Infections in Pregnant Women


Bacteremia; secondary complication: endocarditis,
meningitis, and osteomyelitis, are rare

Infections in Men and Non-Pregnant Women


Bacteremia, pneumonia, bone and joint infections, and skin
and soft tissue infections; mostly among
immunocompromised person

Streptococcus pneumoniae
1. Physiology and Structure
Encapsulated
Older cells decolorise readily and appear Gram
negative
Colonies of encapsulated strains are generally
large (1 - 3 mm) on blood agar; smaller on
chocolatised or heated blood agar, round and
mucoid; colonies of non-encapsulated strains are
smaller and appear flat

Streptococcus pneumoniae

Streptococcus pneumoniae

Streptococcus pneumoniae
The choline is unique to the cell wall of
Streptococcus pneumoniae and plays an important
regulatory role in cell wall hydrolysis
Choline must be present for activity of the
pneumococcal autolysin, amidase, during cell
division
2 forms of teichoic acid: one exposed on the cell
surface and similar form covalently bound to the
plasma membrane lipids

Streptococcus pneumoniae
The lipid bound teichoic acid in the bacterial
cytoplasmic membrane is called F antigen because
it can cross-react with the Forssman surface
antigens on mammalian cells

Streptococcus pneumoniae
2. Pathogenesis and Immunity
Colonisation and migration

Surface protein adhesions and secretory IgA proteases


and pneumolysin (cytotoxin similar to streptolysin O)

Tissue destruction

Pneumolysin, hydrogen peroxide and


phosphorylcholine in the bacterial cell wall

Phagocytic survival

Capsule

Streptococcus pneumoniae
3. Clinical Diseases

Pneumonia
Sinusitis and Otitis media
Meningitis
Bacteremia

Otitis Media