|S. pyogenes bacteria at 900x magnification|
Streptococcus pyogenes is a species of bacteria. Like most other streptococci, it is clinically important in human illness. It is an infrequent, but usually pathogenic, part of the skin flora. It is the predominant species harboring the Lancefield group A antigen, and is often called group A streptococcus (GAS). However, both Streptococcus dysgalactiae and the Streptococcus anginosus group can possess group A antigen. Group A streptococcal infection can cause illness, which typically produces small zones of beta-hemolysis, a complete destruction of red blood cells. (A zone size of 2–3 mm is typical). It is thus also called group A (beta-hemolytic) streptococcus (GABHS).
Like other cocci, streptococci are round bacteria. The name is derived from the Greek meaning pus(pyo)-forming(genes) chain(Strepto) of berries (coccus), because streptococcal cells tend to link together in chains of round cells (see image) and a number of infections caused by it produce pus. Streptococci are catalase-negative and Gram-positive. S. pyogenes can be cultured on blood agar plates. Under ideal conditions, it has an incubation period of 1 to 3 days.
An estimated 700 million GAS infections occur worldwide each year. While the overall mortality rate for these infections is 0.1%, over 650,000 of the cases are severe and invasive, and have a mortality rate of 25%. Early recognition and treatment are critical; diagnostic failure can result in sepsis and death.
In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its M protein, a virulence factor displayed on its surface. Later, in 1946, Lancefield described the serologic classification of S. pyogenes isolates based on their surface T-antigen. Four of the 20 T-antigens have been revealed to be pili, which are used by bacteria to attach to host cells. Over 220 M serotypes and about 20 T serotypes are known.
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. The most striking sign is a strawberry-like rash. 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 life-threatening condition requiring surgery.
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 postinfectious "nonpyogenic" (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 postinfectious 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.
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. A carbohydrate-based bacterial 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. M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. The M protein found on some serotypes is 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.
All strains of S. pyogenes are polylysogenized, in that they carry one or more bacteriophage on their genomes. Some of the phages may be defective, but in some cases active phage may compensate for defects in others. In general, the genome of S. pyogenes strains isolated during disease are >90% identical, they differ by the phage they carry.
|Streptolysin O||An exotoxin, one of the bases of the organism's beta-hemolytic property, streptolysin O causes an immune response and detection of antibodies to it; antistreptolysin O (ASO) can be clinically used to confirm a recent infection.|
|Streptolysin S||A cardiotoxic exotoxin, another beta-hemolytic component, not immunogenic and O2 stable: A potent cell poison affecting many types of cell including neutrophils, platelets, and subcellular organelles.|
|Streptococcal pyrogenic exotoxin A (SpeA)||Superantigens secreted by many strains of S. pyogenes: This pyrogenic exotoxin is responsible for the rash of scarlet fever and many of the symptoms of streptococcal toxic shock syndrome, also known as toxic shock like syndrome(TSLS).|
|Streptococcal pyrogenic exotoxin C (SpeC)|
|Streptokinase||Enzymatically activates plasminogen, a proteolytic enzyme, into plasmin, which in turn digests fibrin and other proteins|
|Hyaluronidase||Hyaluronidase is widely assumed to facilitate 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 capable of secreting hyaluronidase do not appear to need it to spread through tissues or to cause skin lesions. 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 NETs' web of DNA, to which are bound neutrophil serine proteases that can kill the bacteria.|
|C5a peptidase||C5a peptidase cleaves a potent neutrophil chemotaxin called C5a, which is produced by the complement system. C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue. 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.|
|Streptococcal chemokine protease||The affected tissue of patients with severe cases of necrotizing fasciitis are devoid of neutrophils. The serine protease ScpC, which is released by S. pyogenes, is responsible for preventing the migration of neutrophils to the spreading infection. ScpC degrades the chemokine IL-8, which would otherwise attract neutrophils to the site of infection.|
Usually, a throat swab is taken to the laboratory for testing. A Gram stain is performed to show Gram-positive cocci in chains. Then, the organism is cultured on blood agar with an added bacitracin antibiotic disk to show beta-hemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Culture on agar not containing blood, and then performing the catalase test 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.
The rapid pyrrolidonyl arylamidase (PYR) test is used for the presumptive identification of group A beta-hemolytic streptococci. GBS gives a negative finding on this test.
The treatment of choice is penicillin, and the duration of treatment is well established as being 10 days minimum. For toxic shock syndrome and necrotizing fasciitis, high-dose penicillin and clindamycin are used. Additionally, for necrotizing fasciitis, surgery is often needed to remove damaged tissue and stop the spread of the infection.
No instance of penicillin resistance has been reported to date, although since 1985, many reports of penicillin tolerance have been made. The reason for the failure of penicillin to treat S. pyogenes is most commonly patient noncompliance, but in cases where patients have been compliant with their antibiotic regimen, and treatment failure still occurs, another course of antibiotic treatment with cephalosporins is common.
S. pyogenes infections are best prevented through effective hand hygiene. No vaccines are currently available to protect against S. pyogenes infection, although research has been conducted into the development of one. Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and number of people that will be needed for appropriate trials for safety and efficacy of the vaccine.
Many S. pyogenes proteins have unique properties, which have been harnessed in recent years to produce a highly specific "superglue" and a route to enhance the effectiveness of antibody therapy.
The CRISPR system from this organism that is used to recognize and destroy DNA from invading viruses, stopping the infection was appropriated in 2012 for use as a genome-editing tool that could potentially alter any piece of DNA and later RNA.
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