Streptococcus pyogenes and Streptococcal Disease (page 1)

(This chapter has 4 pages)

Kenneth Todar, PhD
Introduction
Streptococcus pyogenes (Group A streptococcus) is a Gram-positive, nonmotile,
nonsporeforming coccus that occurs in chains or in pairs of cells. Individual cells are round-toovoid cocci, 0.6-1.0 micrometer in diameter (Figure 1). Streptococci divide in one plane and thus
occur in pairs or (especially in liquid media or clinical material) in chains of varying lengths. The
metabolism of S. pyogenes is fermentative; the organism is a catalase-negative aerotolerant
anaerobe (facultative anaerobe), and requires enriched medium containing blood in order to grow.
Group A streptococci typically have a capsule composed of hyaluronic acid and exhibit beta (clear)
hemolysis on blood agar.

Figure 1. Streptococcus pyogenes. Left. Gram stain of Streptococcus pyogenes in a

clinical specimen. Right. Colonies of Streptococcus pyogenes on blood agar exhibiting
beta (clear) hemolysis.
Streptococcus pyogenes is one of the most frequent pathogens of humans. It is estimated that
between 5-15% of normal individuals harbor the bacterium, usually in the respiratory tract,
without signs of disease. As normal flora, S. pyogenes can infect when defenses are compromised
or when the organisms are able to penetrate the constitutive defenses. When the bacteria are
introduced or transmitted to vulnerable tissues, a variety of types of suppurative infectionscan
occur.
In the last century, infections by S. pyogenes claimed many lives especially since the organism
was the most important cause of puerperal fever (sepsis after childbirth). Scarlet fever was
formerly a severe complication of streptococcal infection, but now, because of antibiotic therapy, it
is little more than streptococcalpharyngitis accompanied by rash. Similarly, erysipelas (a form of
cellulitis accompanied by fever and systemic toxicity) is less common today. However, there has
been a recent increase in variety, severity and sequelae ofStreptococcus pyogenes infections, and
a resurgence of severe invasive infections, prompting descriptions of "flesh eating bacteria" in
the news media. A complete explanation for the decline and resurgence is not known. Today, the
pathogen is of major concern because of the occasional cases of rapidly progressive disease and
because of the small risk of serious sequelae in untreated infections. These diseases remain a
major worldwide health concern, and effort is being directed toward clarifying the risk and
mechanisms of these sequelae and identifying rheumatogenic and nephritogenic strains of
streptococci.

Acute Streptococcus pyogenes infections may present as pharyngitis (strep throat), scarlet
fever (rash), impetigo (infection of the superficial layers of the skin) or cellulitis (infection of the
deep layers of the skin). Invasive, toxigenic infections can result in necrotizing
fasciitis, myositis and streptococcal toxic shock syndrome. Patients may also develop
immune-mediated post-streptococcal sequelae, such as acute rheumatic fever and
acuteglomerulonephritis, following acute infections caused by Streptococcus pyogenes.
Streptococcus pyogenes produces a wide array of virulence factors and a very large number of
diseases. Virulence factors of Group A streptococci include: (1) M protein, fibronectin-binding
protein (Protein F) and lipoteichoic acid for adherence; (2) hyaluronic acid capsule as an
immunological disguise and to inhibit phagocytosis; M-protein to inhibit phagocytosis
(3) invasins such asstreptokinase, streptodornase (DNase B), hyaluronidase,
and streptolysins; (4) exotoxins, such as pyrogenic (erythrogenic) toxin which causes the
rash ofscarlet fever and systemic toxic shock syndrome.
Classification of Streptococci
Hemolysis on blood agar
The type of hemolytic reaction displayed on blood agar has long been used to classify the
streptococci. Beta -hemolysis is associated with complete lysis of red cells surrounding the
colony, whereas alpha-hemolysis is a partial or "green" hemolysis associated with reduction of
red cell hemoglobin. Nonhemolytic colonies have been termed gamma-hemolytic. Hemolysis is
affected by the species and age of red cells, as well as by other properties of the base
medium. Group A streptococci are nearly always beta-hemolytic; related Group B can
manifest alpha, beta or gamma hemolysis. Most strains of S. pneumoniae are alpha-hemolytic but
can cause -hemolysis during anaerobic incubation. Most of the oral streptococci and enterococci
are non hemolytic. The property of hemolysis is not very reliable for the absolute identification of
streptococci, but it is widely used in rapid screens for identification of S. pyogenes and S.
pneumoniae.
Antigenic types
The cell surface structure of Group A streptococci is among the most studied of any bacteria
(Figure 2). The cell wall is composed of repeating units of N-acetylglucosamine and Nacetylmuramic acid, the standard peptidoglycan. Historically, the definitive identification of
streptococci has rested on the serologic reactivity of "cell wall" polysaccharide antigens as
originally described by Rebecca Lancefield. Eighteen group-specific antigens (Lancefield
groups) were established. The Group A polysaccharide is a polymer of N-acetylglucosamine and
rhamnose. Some group antigens are shared by more than one species. This polysaccharide is also
called the C substance or group carbohydrate antigen.

Streptococcus pyogenes and Streptococcal Disease (page 2)

(This chapter has 4 pages)
Kenneth Todar, PhD
Pathogenesis
Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly
multiply and spread in its host while evading phagocytosis and confusing the immune system.
Acute diseases associated with Streptococcus pyogenes occur chiefly in therespiratory
tract, bloodstream, or the skin. Streptococcal disease is most often a respiratory infection
(pharyngitis or tonsillitis) or a skin infection (pyoderma). Some strains of streptococci show a
predilection for the respiratory tract; others, for the skin. Generally, streptococcal isolates from the
pharynx and respiratory tract do not cause skin infections. Figure 3 describes the pathogenesis
of S. pyogenes infections.
S. pyogenes is the leading cause of uncomplicated bacterial pharyngitis andtonsillitis commonly
referred to a strep throat. Other respiratory infections include sinusitis, otitis,
and pneumonia.
Infections of the skin can be superficial (impetigo) or deep (cellulitis). Invasive streptococci
cause joint or bone infections, destructive wound infections (necrotizing fasciitis)
and myositis, meningitis andendocarditis. Two post streptococcal sequelae, rheumatic
fever andglomerulonephritis, may follow streptococcal disease, and occur in 1-3% of untreated
infections. These conditions and their pathology are not attributable to dissemination of bacteria,
but to aberrent immunological reactions to Group A streptococcal antigens. Scarlet
fever and streptococcal toxic shock syndromeare systemic responses to circulating bacterial
toxins.
The cell surface of Streptococcus pyogenes accounts for many of the bacterium's determinants of
virulence, especially those concerned with colonization and evasion of phagocytosis and the host
immune responses. The surface of Streptococcus pyogenes is incredibly complex and chemicallydiverse. Antigenic components include capsular polysaccharide (C-substance), cell
wall peptidoglycan and lipoteichoic acid (LTA), and a variety of surface proteins, including M
protein, fimbrial proteins, fibronectin-binding proteins, (e.g. Protein F) and cellbound streptokinase.
The cytoplasmic membrane of S. pyogenes contains some antigens similar to those of human
cardiac, skeletal, and smooth muscle, heart valve fibroblasts, and neuronal tissues, resulting
in molecular mimicry and a tolerant or suppressed immune response by the host.
The cell envelope of a Group A streptococcus is illustrated in Figure 2. The complexity of the
surface can be seen in several of the electron micrographs of the bacterium that accompany this
article.

Figure 2. Cell surface structure of Streptococcus pyogenes and secreted products

involved in virulence.
In Group A streptococci, the R and T proteins are used as epidemiologic markers and have no
known role in virulence. The group carbohydrate antigen (composed of N-acetylglucosamine and
rhamnose) has been thought to have no role in virulence, but emerging strains with increased
invasive capacity produce a very mucoid colony, suggesting a role of the capsule in virulence.
The M proteins are clearly virulence factors associated with both colonization and resistance to
phagocytosis. More than 50 types of S. pyogenes M proteins have been identified on the basis of
antigenic specificity, and it is the M protein that is the major cause of antigenic shift and antigenic
drift in the Group A streptococci. The M protein (found in fimbriae) also binds fibrinogen from
serum and blocks the binding of complement to the underlying peptidoglycan. This allows survival
of the organism by inhibiting phagocytosis.
The streptococcal M protein, as well as peptidoglycan, N-acetylglucosamine, and group-specific
carbohydrate, contain antigenic epitopes that mimic those of mammalian muscle and connective
tissue. As mentioned above, the cell surface of recently emerging strains of streptococci is
distinctly mucoid (indicating that they are highly encapsulated). These strains are also rich in
surface M protein. The M proteins of certain M-types are considered rheumatogenic since they
contain antigenic epitopes related to heart muscle, and they therefore may lead to autoimmune
rheumatic carditis (rheumatic fever) following an acute infection.
The Hyaluronic Acid Capsule
The capsule of S. pyogenes is non antigenic since it is composed of hyaluronic acid, which is
chemically similar to that of host connective tissue. This allows the bacterium to hide its own

antigens and to go unrecognized as antigenic by its host. The Hyaluronic acid capsule also
prevents opsonized phagocytosis by neutrophils or mancrophages.
Adhesins
Colonization of tissues by S. pyogenes is thought to result from a failure in the constitutive
defenses (normal flora and other nonspecific defense mechanisms) which allows establishment of
the bacterium at a portal of entry (often the upper respiratory tract or the skin) where the
organism multiplies and causes an inflammatory purulent lesion.
It is now realized that S. pyogenes (like many other bacterial pathogens) produces multiple
adhesins with varied specificities. There is evidence thatStreptococcus
pyogenes utilizes lipoteichoic acids (LTA), M protein, and multiple fibronectin-binding
proteins in its repertoire of adhesins. LTA is anchored to proteins on the bacterial surface,
including the M protein. Both the M proteins and lipoteichoic acid are supported externally to the
cell wall on fimbriae and appear to mediate bacterial adherence to host epithelial cells. The
fibronectin-binding protein, Protein F, has also been shown to mediate streptococcal adherence to
the amino terminus of fibronectin on mucosal surfaces.
Identification of Streptococcuspyogenes adhesins has long been a subject of conflict and debate.
Most of the debate was between proponents of the LTA model and those of the M protein model. In
1972, Gibbons and his colleagues proposed that attachment of streptococci to the oral mucosa of
mice is dependent on M protein. However, Olfek and Beachey argued that lipoteichoic acid (LTA),
rather than M protein, was responsible for streptococcal adherence to buccal epithelial cells. In
1996, Hasty and Courtney proposed a two-step model of attachment that involved both M protein
and teichoic acids. They suggested that LTA loosely tethers streptococci to epithelial cells, and then
M protein and/or other fibronectin (Fn)-binding proteins secure a firmer, irreversible association.
The first streptococcal fibronectin-binding protein (Sfb) was demonstrated in 1992. Shortly
thereafter, protein F was discovered. Most recently (1998), the M1 and M3 proteins were shown to
bind fibronectin.
Extracellular products: invasins and exotoxins
Colonization of the upper respiratory tract and acute pharyngitis may spread to other portions of
the upper or lower respiratory tracts resulting in infections of the middle ear (otitis media), sinuses
(sinusitis), or lungs (pneumonia). In addition, meningitis can occur by direct extension of infection
from the middle ear or sinuses to the meninges or by way of bloodstream invasion from the
pulmonary focus. Bacteremia can also result in infection of bones (osteomyelitis) or joints
(arthritis). During these aspects of acute disease the streptococci bring into play a variety of
secretory proteins that mediate their invasion.
For the most part, streptococcal invasins and protein toxins interact with mammalian blood and
tissue components in ways that kill host cells and provoke a damaging inflammatory response. The
soluble extracellular growth products and toxins of Streptococcus pyogenes (see Figure 2, above),
have been studied intensely. Streptolysin S is an oxygen-stable leukocidin; Streptolysin O is an
oxygen-labile leukocidin. NADase is also leukotoxic. Hyaluronidase (the original "spreading
factor") can digest host connective tissue hyaluronic acid, as well as the organism's own
capsule. Streptokinases participate in fibrin lysis.Streptodornases A-D possess
deoxyribonuclease activity; Streptodornases B and D possess ribonuclease activity as
well. Protease activity similar to that inStaphylococcus aureus has been shown in strains causing
soft tissue necrosis or toxic shock syndrome. This large repertoire of products is important in the

pathogenesis of S. pyogenes infections. Even so, antibodies to these products are relatively
insignificant in protection of the host.
The streptococcal invasins act in a variety of ways summarized in Table 1 at the end of this article.
Streptococcal invasins lyse eukaryotic cells, including red blood cells and phagocytes; they lyse
other host macromolecules, including enzymes and informational molecules; they allow the
bacteria to spread among tissues by dissolving host fibrin and intercellular ground substances.
Pyrogenic Exotoxins
Three streptococcal pyrogenic exotoxins (SPE), formerly known asErythrogenic toxin, are
recognized: types A, B, C. These toxins act assuperantigens by a mechanism similar to those
described for staphylococci. As antigens, they do not requiring processing by antigen presenting
cells. Rather, they stimulate T cells by binding class II MHC molecules directly and nonspecifically.
With superantigens about 20% of T cells may be stimulated (vs 1/10,000 T cells stimulated by
conventional antigens) resulting in massive detrimental cytokine release. SPE A and SPE C are
encoded by lysogenic phages; the gene for SPE B is located on the bacterial chromosome.
The erythrogenic toxin is so-named for its association with scarlet fever which occurs when the
toxin is disseminated in the blood. Re-emergence in the late 1980's of exotoxin-producing strains
of S. pyogenes has been associated with atoxic shock-like syndrome similar in pathogenesis
and manifestation to staphylococcal toxic shock syndrome, and with other forms of invasive
disease associated with severe tissue destruction. The latter condition is termednecrotizing
fasciitis. Outbreaks of sepsis, toxic shock and necrotizing fasciitis have been reported at
increasing frequency. The destructive nature of wound infections prompted the popular press to
refer to S. pyogenes as "flesh-eating bacteria" and "skin-eating streptococci". The increase in
invasive streptococcal disease was associated with emergence of a highly virulent serotype M1
which is disseminated world-wide. The M1 strain produces the erythrogenic toxin (Spe A), thought
to be responsible for toxic shock, and the enzyme cysteine protease which is involved in tissue
destruction. Because clusters of toxic shock were also associated with other serotypes, particularly
M3 strains, it is believed that unidentified host factors may also have played an important role in
the resurgence of these dangerous infections.

FIGURE 3. Pathogenesis of Streptococcus pyogenes infections. Adapted from Baron's

Medical Microbiology Chapter 13, Streptococcus by Maria Jevitz Patterson.

Streptococcus pyogenes and Streptococcal Disease (page 3)

(This chapter has 4 pages)
Kenneth Todar, PhD
Post streptococcal sequelae
Infection with Streptococcus pyogenes can give rise to serious nonsuppurative sequelae:
acute rheumatic fever and acute glomerulonephritis. These pathological events begin 1-3
weeks after an acute streptococcal illness, a latent period consistent with an immune-mediated
etiology. Whether all S. pyogenesstrains are rheumatogenic is controversial; however, clearly not
all strains are nephritogenic.
Acute rheumatic fever is a sequel only of pharyngeal infections, but
acuteglomerulonephritis can follow infections of the pharynx or the skin. Although there is no
adequate explanation for the precise pathogenesis of acute rheumatic fever, an abnormal or
enhanced immune response seems essential. Also, persistence of the organism on pharyngeal
tissues (i.e., the tonsils) is associated with an increased likelihood of rheumatic fever. Acute
rheumatic fever can result in permanent damage to the heart valves. Less than 1% of sporadic
streptococcal pharyngitis infections result in acute rheumatic fever; however, recurrences are
common, and life-long antibiotic prophylaxis is recommended following a single case.
The occurrence of cross-reactive antigens in S. pyogenes and heart tissues possibly explains the
autoimmune responses that develop following some infections. The antibody mediated immune
(AMI) response (i.e., level of serum antibody) is higher in patients with rheumatic fever than in
patients with uncomplicated pharyngitis. In addition, cell-mediated immunity (CMI) seems to play
a role in the pathology of acute rheumatic fever.
Acute glomerulonephritis results from deposition of antigen-antibody-complement complexes on
the basement membrane of kidney glomeruli. The antigen may be streptococcal in origin or it may
be a host tissue species with antigenic determinants similar to those of streptococcal antigen
(cross-reactive epitopes for endocardium, sarcolemma, vascular smooth muscle). The incidence of
acute glomerulonephritis in the United States is variable, perhaps due to cycling of nephritogenic
strains, but it appears to be decreasing. Recurrences are uncommon, and prophylaxis following an
initial attack is unnecessary.
Host defenses
S. pyogenes is usually an exogenous secondary invader, following viral disease or disturbances
in the normal bacterial flora. In the normal human the skin is an effective barrier against invasive
streptococci, and nonspecific defense mechanisms prevent the bacteria from penetrating beyond
the superficial epithelium of the upper respiratory tract. These mechanisms include mucociliary
movement, coughing, sneezing and epiglottal reflexes.
The host phagocytic system is a second line of defense against streptococcal invasion.
Organisms can be opsonized by activation of the classical or alternate complement pathway and by
anti-streptococcal antibodies in the serum. S. pyogenes is rapidly killed following phagocytosis
enhanced by specific antibody. The bacteria do not produce catalase or significant amounts of
superoxide dismutase to inactivate the oxygen metabolites (hydrogen peroxide, superoxide)
produced by the oxygen-dependent mechanisms of the phagocyte. Therefore, they are quickly

killed after engulfment by phagocytes. The streptococcal defense must be one to stay out of
phagocytes.
In immune individuals, IgG antibodies reactive with M protein promote phagocytosis which results
in killing of the organism. This is the major mechanism by which AMI is able to terminate Group A
streptococcal infections.M protein vaccines are a major candidate for use against rheumatic
fever, but certain M protein types cross-react antigenically with the heart and themselves may be
responsible for rheumatic carditis. This risk of autoimmunity has prevented the use of Group A
streptococcal vaccines. However, since the cross-reactive epitopes of the M-protein are now
known, it appears that limited anti-streptococcal vaccines are on the horizon.

FIGURE 4. Phagocytosis of Streptococcus pyogenes by a macrophage.CELLS alive!

The hyaluronic acid capsule allows the organism to evade opsonization. The capsule is also an
antigenic disguise that hides bacterial antigens and is non antigenic to the host. Actually, the
hyaluronic acid outer surface of S. pyogenesis weakly antigenic, but it does not result in
stimulation of protective immunity. The only protective immunity that results from infection by
Group A streptococcus comes from the development of type-specific antibody to the M protein of
the fimbriae, which protrude from the cell wall through the capsular structure. This antibody, which
follows respiratory and skin infections, is persistent. Presumably, protective levels of specific IgA is
produced in the respiratory secretions while protective levels of IgG are formed in the serum.
Sometimes, intervention of an infection with effective antibiotic treatment precludes the
development of this persistent antibody. This accounts, in part, for recurring infections in an
individual by the same streptococcal strain. Antibody to the erythrogenic toxin involved in scarlet
fever is also long lasting.
Treatment and prevention
Penicillin is still uniformly effective in treatment of Group A streptococcal disease. It is important to
identify and treat Group A streptococcal infections in order to prevent sequelae. No effective
vaccine has been produced, but specific M-protein vaccines are being tested.

Table 1. Summary of virulence determinants of Streptococcus pyogenes

Adherence (colonization) surface macromolecules
M protein
Lipoteichoic acid (LTA)
Protein F and Sfb (fibronectin-binding proteins)

Enhancement of spread in tissues

Hyaluronidase hydrolyses hyaluronic acid, part of the ground substance in host tissues.
Proteases
Streptokinase lyses fibrin
Evasion of phagocytosis
Capsule: hyaluronic acid is produced.
C5a peptidase: C5a enhances chemotaxis of phagocytes .
M protein is a fibrillar surface protein. Its distal end bears a negative charge that interferes with
phagocytosis. It also blocks complement deposition on the cell surface. Mutations during the
course of infection alter the structure of M proteins, rendering some antibodies ineffective. Strains
that persist in carriers frequently exhibit altered M proteins.
Leukocidins, including streptolysin S and streptolysin O, are proteins secreted by the streptococci
to kill phagocytes (and probably to release nutrients for their growth)
Defense against host immune responses
Antigenic disguise and tolerance provided by hyaluronic acid capsule
Antigenic variation. Antibody against M protein (antigen) is the only effective protective antibody,
but there are more than 50 different M types, and subsequent infections may occur with a different
M serotype.
Production of toxins and other systemic effects
Toxic shock: Exotoxin is superantigen that binds directly to MHC II (without being processed) and
binds abnormally to the T cell receptor of many (up to 20% of) T cells. Exaggerated production of
cytokines causes the signs of shock: fever, rash, low blood pressure. aberrant interaction between
toxin, macrophage, and T cells.
Induction of circulating, cross-reactive antibodies
Some of the antibodies produced during infection by certain strains of streptococci cross-react with
certain host tissues. These antibodies can indirectly damage host tissues, even after the organisms
have been cleared, and cause autoimmune complications.

Table 2. Summary of diseases caused by Streptococcus pyogenes

Suppurative conditions (active infections associated with pus) occur in the throat, skin, and
systemically.
Throat
Streptococcal pharyngitis is acquired by inhaling aerosols emitted by infected individuals. The
symptoms reflect the inflammatory events at the site of infection. A few (1-3%) people develop
rheumatic fever weeks after the infection has cleared.

Skin
Impetigo involves the infection of epidermal layers of skin. Pre-pubertal children are the most
susceptible. Cellulitis occurs when the infection spreads subcutaneous tissues. Erysipelas is the
infection of the dermis. About 5% of patients will develop more disseminated disease. Necrotizing
fasciitis involves infection of the fascia and may proceed rapidly to underlying muscle.
Systemic
Scarlet fever is caused by production of erythrogenic toxin by a few strains of the organism.
Toxic shock is caused by a few strains that produce a toxic shock-like toxin.
Non-suppurative Sequelae
Some of the antibodies produced during the above infections cross-react with certain host tissues.
These can indirectly damage host tissues, even after the organisms have beencleared, and cause
non suppurative complications.
Rheumatic fever. M protein cross reacts with sarcolemma. Antibodies cross-react with heart tissue,
fix complement, and cause damage.
Glomerulonephritis. Antigen-antibody complexes may be deposited in kidney, fix complement, and
damage glomeruli. Only a few M-types are nephritogenic.

Streptococcus pyogenes and Streptococcal Disease (page 4)

(This chapter has 4 pages)
Kenneth Todar, PhD
Gallery of electron micrographs of Streptococcus pyogenes from The Laboratory of
Pathogenesis and Immunology at Rockefeller University, the home of research
on Streptococcus pyogenes

Critical point dried whole group A streptococci (Streptococcus pyogenes) viewed directly
by transmission electron microscopy (TEM 6,500X). Chains of streptococci are clearly
evident. To remove cell surface proteins, cells were treated with trypsin prior to
preparation and mounting. Strain: D471; M-type 6. Electron micrograph
of Streptococcus pyogenes by Maria Fazio and Vincent A. Fischetti, Ph.D. with
permission. The Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller
University.

Dividing streptococci (12,000X). Electron micrograph of Streptococcus pyogenes by

Maria Fazio and Vincent A. Fischetti, Ph.D. with permission.The Laboratory of Bacterial
Pathogenesis and Immunology, Rockefeller University.

Electron micrograph of an ultra-thin section of a chain of group A streptococci

(20,000X). The cell surface fibrils, consisting primarily of M protein, are clearly evident.
The bacterial cell wall, to which the fibrils are attached, is also clearly seen as the light
staining region between the fibrils and the dark staining cell interior. Incipient cell
division is also indicated by the nascent septum formation (seen as an indentation of the
cell wall) near the cell equator. The streptococcal cell diameter is equal to approximately
one micron. Electron micrograph of Streptococcus pyogenes by Maria Fazio and Vincent
A. Fischetti, Ph.D. with permission.The Laboratory of Bacterial Pathogenesis and
Immunology, Rockefeller University.

Negative staining of group A streptococci viewed by TEM 28,000X. The "halo" around the
chain of cells (approximately equal in thickness to the cell diameter) is the remnants of
the capsule that may be found surrounding the exterior of certain strains of group A

streptococci. The septa between pairs of dividing cells may also be seen. Electron
micrograph of Streptococcus pyogenes by Maria Fazio and Vincent A. Fischetti, Ph.D.
with permission. The Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller
University.

High magnification electron micrograph of an ultra-thin section of a group A

streptococcus sibling pair (70,000 X). At this magnification, especially in the cell on the
left, the cell wall and cell surface fibrils, consisting primarily of M protein, are well
defined. Interdigitaion of these fibrils between neighboring cells of different chains is
also in plain view. Strain: C126/21/1; M-type 43. Electron micrograph of Streptococcus
pyogenes by Maria Fazio and Vincent A. Fischetti, Ph.D. with permission.The Laboratory
of Bacterial Pathogenesis and Immunology, Rockefeller University.

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