Dr Alvin Fox
Medical Microbiology, MBIM
650/720 Lecture: 38
Streptococci are facultative
anaerobic, Gram-positive organisms that often occur as chains or pairs
and are catalase-negative
(staphylococci are catalase positive). Streptococci are subdivided into
groups by antibodies that recognize surface antigens. These groups may
include one or more species. The most important groupable streptococci
are A, B and D. Among the groupable streptococci, infectious disease
(particularly pharyngitis) is caused by group A which is thus emphasized
here. Streptococcus pneumoniae (a major cause of human pneumonia)
and Streptococcus mutans and other so-called viridans
streptococci (among the causes of dental caries) do not possess group
Streptococcus mutans. Gram stain. CDC/Dr. Richard Facklam
Three types of hemolysis reaction
are seen after growth of streptococci on sheep blood agar (alpha, beta,
gamma). alpha refers to partial hemolysis with a green coloration (from
production of an unidentified product of hemoglobin) seen around the
colonies; beta refers to complete clearing and gamma means there is no
lysis. Group A and group B streptococci are beta hemolytic, whilst D are
usually alpha or gamma. Streptococcus pneumoniae and viridans
("green") streptococci are a hemolytic. Thus the hemolysis
reaction is important in grouping streptococci. The hemolysis reaction
along with one physiologic characteristic is sufficient for a
presumptive clinical identification.
Group A streptococcus (S.
Streptococcus pyogenes - coccoid prokaryote (dividing); causes
pharyngitis, sinusitis, otitis media (middle ear infection), food
poisoning, puerperal fever (childbed fever), skin and wound infections
(scarlet fever, erysipelas, impetigo) . Group A strep. SEM x56,000
© Dr Dennis
Kunkel, University of Hawaii. Used with permission
Information sheet Group A Streptococcal (GAS) Disease
Group A Streptococcal Infections Associated with Asymptomatic
Health-Care Workers -- Maryland and California, 1997 (from
This organism traditionally
but non-invasive pharyngitis, and less frequently the skin infection,
impetigo. In the middle part of the 1900's, the serious complications of
group A streptococcal infections began to decline dramatically and had
greatly decreased by the 70's. Thus, interest in this organism waned. In
the 80's and 90's, there has been an upsurge in classical
"rheumatic fever" (a non-suppurative disease of the heart) but
also new forms of streptococcal disease which includes both
"invasive" bacteremia, a toxic shock-like syndrome (as seen
with S. aureus) and so-called "flesh eating" bacteria.
Group A streptococcal infections
affect all ages with peak incidence at 5-15 years of age. The serious
complications (including rheumatic fever and invasive bacteremia) were
felt to affect primarily those with some underlying defect in their
immune system (including infants, elderly people and those
immunocompromised). However, it is clear now that previously healthy
children and adults are definitely at risk of serious complications.
Rheumatic fever, is an inflammatory disease affecting primarily the
heart and joints. Although severe it can take an extended period of time
to develop. The mechanism of chronic immunopathology of rheumatic fever
is not resolved. M protein cross-reacts with heart myosin leading to
autoimmunity. Also the group A streptococcal cell wall is highly
resistant to degradation in the host. These antigens persist for months in
vivo and experimentally elicit diseases that resemble rheumatic
arthritis and carditis. Rheumatic arthritis should not be confused with
the most common rheumatic disease - rheumatoid arthritis. Early
termination of throat infections with penicillin therapy decreases the
incidence of the subsequent development of rheumatic carditis.
is an immune complex disease of the kidney.
The characteristic rash is caused by erythrogenic (pyrogenic) toxins
which are phage encoded.
Bacteremia and toxic-shock.
The newly described invasive (and sometimes fatal) forms of the disease
with a toxic shock-like disease (including rash, fever and shifting of
fluid from the bloodstream to peripheral tissues with resulting edema)
and/or necrotizing myositis and fasciitis. Production of pyrogenic
toxins (A, B and C) are a hallmark of these strains. Pyrogenic toxin is
a superantigen (a mitogen) for T cells causing non-specific activation
of the immune system. This may be involved in the pathogenesis. This
disease is still uncommon but can progress very quickly (a few days) and
General features in
The identity of the adhesin
allowing adhesion to the respiratory epithelium (via fibronectin) is
somewhat controversial. Lipoteichoic acid is localized in the cell
membrane of many bacteria. For group A streptococci, much is also
present in the fimbriae on the cell exterior. Classical work suggests
lipoteichoic acid is the group A streptococcal adhesin although more
recently a role for an "F (fibronectin-binding) protein" has
Group A streptococci in the
absence of fibrinogen fix complement to the peptidoglycan layer and, in
the absence of antibodies, are not phagocytosed. The M protein (also
found in fimbriae) binds fibrinogen from serum and blocks the binding of
complement to the underlying peptidoglycan. This allows survival of the
organism by inhibiting phagocytosis. However, in immune individuals,
neutralizing antibodies reactive with M protein elicit phagocytosis
which results in killing of the organism. This is the major mechanism by
which immunity is able to terminate group A streptococcal infections. M
protein vaccines are thus a major candidate for use against rheumatic
fever. The capsule of group A streptococci classically was stated to
have limited anti-phagocytic activity. Many of the newly described
virulent strains are highly mucoid and the capsules are important in
Unfortunately, certain M protein
types cross-react antigenically with the heart and may be responsible
for rheumatic carditis. The fear of autoimmunity has rightly inhibited
the use of group A streptococcal vaccines. However, distinct protective
versus cross-reactive epitopes have been defined and the availability of
a vaccine appears likely. M proteins vary antigenically between strains;
thus immunity to one M protein does not imply general immunity to all S.
pyogenes strains. M typing along with other antigens (T and R) are
used for serotyping.
1. Direct detection - the antigen
is extracted from a throat swab. The antigen extract will then bind with
antibody specific to the group A streptococcal carbohydrate. This has
classically involved agglutination of antibody coated beads. However,
simpler tests have been recently introduced. Results are available
2. Lancefield grouping of
isolated beta hemolytic colonies (see above).
3. Colonies are beta hemolytic
and their growth is inhibited by bacitracin (presumptive diagnosis).
4. Patient serum shows antibodies
to streptolysin O or other streptococcal antigens. This is important if
delayed clinical sequelae occur.
ß hemolysis is caused by
two hemolysins O and S; the former is inactive in the presence of
oxygen. Thus, stabbing of the plate increases the intensity of the
Group B streptococcus (S.
These organisms cause neonatal
meningitis and septicemia after transmission from the normal vaginal
flora of the mother.
The organism can be identified on
the basis of beta hemolysis, hydrolysis of hippurate and the CAMP
reaction. CAMP is an abbreviation for the names of the 4 individuals who
originally described the test. Group B streptococci produce a factor
that increases ß hemolysis of an S. aureus indicator
Group D streptococcus
Growth on bile-esculin produces a
black precipitate derived from esculin; many other bacteria will not
grow in the presence of bile. Group D streptococci are divided into
those that will grow in 6.5% saline (enterococci) and those that will
not (non-enterococci). Enterococci much more commonly cause human
disease than non-enterococci. Enterococci are often resistant to
penicillin. Enterococci are distantly related to other streptococci and
have been moved into the genus Enterococcus; the most commonly
isolated is E. (S.) faecalis. As the name implies enterococci are
found in the gut flora and infection often follows from fecal
contamination. A significant cause of urinary tract infections (much
less common than E. coli) and also opportunistic infections
(including intra-abdominal, septicemia and endocarditis). Colonies are
usually alpha or gamma hemolytic.
Streptococcus faecalis - coccoid prokaryote (dividing); a pathogen
causing skin and wound infections ©
Dr Dennis Kunkel, University of Hawaii. Used with permission
Other beta hemolytic groups
Groups C and G (and rarely group
F) occasionally cause human disease (particularly pharyngitis).
Minute colony streptococci
The normal human flora contains
organisms that may be group A, C, F or G or are non-groupable (S.
anginosus/S. milleri). Their role in human disease is
A diverse group of species
commonly found orally (including S. mutans). Cause
endocarditis after release into the bloodstream from tooth extraction.
They are also involved in dental caries. Are alpha hemolytic and
negative for other tests described above. They are non-groupable.