Streptococcus pyogenes

Streptococcus pyogenes is a spherical gram-positive bacteria that grows in long chains ^[1] and is the cause of Group A streptococcal infections. S. pyogenes displays group A antigen on its cell wall and beta-hemolysis when cultured on blood agar plate. S. pyogenes typically produces large zones of beta-hemolysis, the complete disruption of erythrocytes and the release of hemoglobin, and it is therefore called Group A (beta-hemolytic) Streptococcus (abbreviated GAS). Streptococci are catalase-negative.

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Serotyping

In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its M protein, a virulence factor that is displayed on its surface.^[2] Later in 1946, Lancefield described the serologic classification of S. pyogenes isolates based on their surface T antigen.^[3] Four of the 20 T antigens have been revealed to be pili, which are used by bacteria to attach to host cells.^[4] Currently, over 100 M serotypes and approximately 20 T serotypes are known.

Pathogenesis

Main article: Group A streptococcal infection

S. pyogenes is the cause of many important human diseases ranging from mild superficial skin infections to life-threatening systemic diseases. Infections typically begin in the throat or skin. Examples of mild S. pyogenes infections include pharyngitis ("strep throat") and localized skin infection ("impetigo"). Erysipelas and cellulitis are characterized by multiplication and lateral spread of S. pyogenes in deep layers of the skin. S. pyogenes invasion and multiplication in the fascia can lead to necrotizing fasciitis, a potentially life-threatening condition requiring surgical treatment.

Infections due to certain strains of S. pyogenes can be associated with the release of bacterial toxins. Throat infections associated with release of certain toxins lead to scarlet fever. Other toxigenic S. pyogenes infections may lead to streptococcal toxic shock syndrome, which can be life-threatening.

S. pyogenes can also cause disease in the form of post-infectious "non-pyogenic" (not associated with local bacterial multiplication and pus formation) syndromes. These autoimmune mediated complications follow a small percentage of infections and include rheumatic fever and acute poststreptococcal glomerulonephritis. Both conditions appear several weeks following the initial streptococcal infection. Rheumatic fever is characterised by inflammation of the joints and/or heart following an episode of Streptococcal pharyngitis. Acute glomerulonephritis, inflammation of the renal glomerulus, can follow Streptococcal pharyngitis or skin infection.

This bacterium remains acutely sensitive to penicillin. Failure of treatment with penicillin is generally attributed to other local commensal organisms producing β-lactamase or failure to achieve adequate tissue levels in the pharynx. Certain strains have developed resistance to macrolides, tetracyclines and clindamycin.

Virulence factors

S. pyogenes has several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.^[5] A carbohydrate capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells.^[6] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. M protein found on some serotypes are also able to prevent opsonization by binding to fibrinogen. However, the M protein is also the weakest point in this pathogen's defense as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes. M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.

S. pyogenes releases a number of proteins, including several virulence factors, into its host:

Streptolysin O and S

These are toxins which are the basis of the organism's beta-hemolytic property. Streptolysin O is a potent cell poison affecting many types of cell including neutrophils, platelets, and sub-cellular organelles. It causes an immune response and detection of antibodies to it; antistreptolysin O (ASO) can be clinically used to confirm a recent infection. Streptolysin O is cardiotoxic.

Streptococcal pyrogenic exotoxins (Spe) A and C

SpeA and SpeC are superantigens secreted by many strains of S. pyogenes. These pyogenic exotoxins are responsible for the rash of scarlet fever and many of the symptoms of streptococcal toxic shock syndrome.

Streptokinase

Enzymatically activates plasminogen, a proteolytic enzyme, into plasmin which in turn digests fibrin and other proteins.

Hyaluronidase

It is widely assumed that hyaluronidase facilitates the spread of the bacteria through tissues by breaking down hyaluronic acid, an important component of connective tissue. However, very few isolates of S. pyogenes are capable of secreting active hyaluronidase due to mutations in the gene that encode the enzyme. Moreover, the few isolates that are capable of secreting hyaluronidase do not appear to need it to spread through tissues or to cause skin lesions.^[7] Thus, the true role of hyaluronidase in pathogenesis, if any, remains unknown.

Streptodornase

Most strains of S. pyogenes secrete up to four different DNases, which are sometimes called streptodornase. The DNases protect the bacteria from being trapped in neutrophil extracellular traps (NETs) by digesting the NET's web of DNA, to which are bound neutrophil serine proteases that can kill the bacteria.^[8]

C5a peptidase

C5a peptidase cleaves a potent neutrophil chemotaxin called C5a, which is produced by the complement system.^[9] C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.^[10]

Streptococcal chemokine protease

The affected tissue of patients with severe cases of necrotizing fasciitis are devoid of neutrophils.^[11] The serine protease ScpC, which is released by S. pyogenes, is responsible for preventing the migration of neutrophils to the spreading infection.^[12] ScpC degrades the chemokine IL-8, which would otherwise attract neutrophils to the site of infection. C5a peptidase, although required to degrade the neutrophil chemotaxin C5a in the early stages of infection, is not required for S. pyogenes to prevent the influx of neutrophils as the bacteria spread through the fascia.^[10][12]

Diagnosis

Usually, a throat swab is taken to the laboratory for testing. A Gram stain is performed to show Gram positive, cocci, in chains. Then, culture the organism on blood agar with added bacitracin antibiotic disk to show beta-haemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Then, perform catalase test, which should show a negative reaction for all Streptococci. S. pyogenes is cAMP and hippurate tests negative. Serological identification of the organism involves testing for the presence of group A specific polysaccharide in the bacterium's cell wall using the Phadebact test. As a precautionary measure tests are also carried out to check for illnesses including, but not limited to, Syphilis, and Avascular Necrosis, and Clubfoot.

Treatment

The treatment of choice is penicillin, however in the absence of readily available penicillin, small incisions made to the infected area will relieve swelling and discomfort until proper medical assistance can be sought. There is no reported instance of penicillin-resistance reported to date, although since 1985 there have been many reports of penicillin-tolerance.^[13]

Macrolides, chloramphenicol, and tetracyclines may be used if the strain isolated has been shown to be sensitive, but resistance is much more common.

References

Other reading

• Gladwin, Mark and Bill Trattler. Clinical Microbiology Made Ridiculously Simple, 3rd edition, 2004.
• Brooks, Geo F., Janet S. Butel, and Stephen A. Morse. Jawetz, Melnick, and Adelberg's Medical Microbiology, 22nd edition, 2001.