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Tag words: Streptococcus, Streptococcus pyogenes, S pyogenes, strep, Group A strep, GAS, strep throat, streptococcal streptococci, Gram-positive cocci, cocci, wound infection, acute rheumatic fever, acute glomerulonephritis, scarlet fever, pharyngitis, impetigo, tonsillitis, pharyngeal cellulitis, pharyngeal abscess, otitis media, sinusitis, necrotizing fasciitis, streptococcal bacteremia, meningitis, brain abscess, gangrene

Streptococcus pyogenes

Kingdom: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Streptococcus
Species: S. pyogenes

Common References: Streptococcus, Streptococcus pyogenes, S pyogenes, strep, Group A strep, GAS, strep throat, Streptococcus pyogenes

Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interest include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Streptococcus pyogenes and Streptococcal Disease (page 2)

(This chapter has 4 pages)

© Kenneth Todar, PhD


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 the respiratory 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 and tonsillitis 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 and endocarditis. Two post streptococcal sequelae, rheumatic fever and glomerulonephritis, 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 syndrome are 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 chemically-diverse. 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 cell-bound 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.


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 that Streptococcus 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 in Staphylococcus 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 as Erythrogenic toxin, are recognized: types A, B, C. These toxins act as superantigens 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 a toxic 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 termed necrotizing 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.

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Kenneth Todar has taught microbiology to undergraduate students at The University of Texas, University of Alaska and University of Wisconsin since 1969.

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