Streptococcus pyogenes

Streptococcus pyogenes
Most streptococci that contain the group A antigen are S pyogenes. It is a prototypical human pathogen. S pyogenes is the main human pathogen associated with local or systemic invasion and poststreptococcal immunologic disorders. S pyogenes typically produces large (1 cm in diameter) zones of beta hemolysis around colonies greater than 0.5 mm in diameter. They are PYR-positive (hydrolysis of L-pyrrolidonyl-2-naphthylamide) and usually are susceptible to bacitracin.
Morphology & Identification
Typical Organisms
Individual cocci are spherical or ovoid and are arranged in chains The cocci divide in a plane perpendicular to the long axis of the chain. The members of the chain often have a striking diplococcal appearance, and rod-like forms are occasionally seen. Streptococci are gram-positive; Most group A strains produce capsules composed of hyaluronic acid. The capsules are most noticeable in very young cultures. They impede phagocytosis. Capsules of other streptococci (eg, S agalactiae and S pneumoniae) are different. The S pyogenes cell wall contains proteins (M, T, R antigens), carbohydrates (group-specific), and peptidoglycans. Hair-like pili project through the capsule of group A streptococci. The pili consist partly of M protein and are covered with lipoteichoic acid. The latter is important in the attachment of streptococci to epithelial cells.
Antigenic Structure
M Protein
This substance is a major virulence factor of group A S pyogenes. M protein appears as hair-like projections of the streptococcal cell wall. When M protein is present, the streptococci are virulent, and in the absence of M type-specific antibodies, they are able to resist phagocytosis by polymorphonuclear leukocytes. S pyogenes that lack M protein are not virulent. There are two major structural classes of M protein, classes I and II.
It appears that M protein and perhaps other streptococcal cell wall antigens have an important role in the pathogenesis of rheumatic fever.
T Substance
This antigen has no relationship to virulence of streptococci. Unlike M protein, T substance is acid-labile and heat-labile. It is obtained from streptococci by proteolytic digestion, another surface antigen has been called R protein.
Nucleoproteins
Extraction of streptococci with weak alkali yields mixtures of proteins and other substances of little serologic specificity, called P substances, which probably make up most of the streptococcal cell body.
Toxins & Enzymes
More than 20 extracellular products that are antigenic are elaborated by S pyogenes, including the following.
Streptokinase (Fibrinolysin)
Streptokinase is produced by many strains of group A beta -hemolytic streptococci. It transforms the plasminogen of human plasma into plasmin, an active proteolytic enzyme that digests fibrin and other proteins.
Streptodornase
Streptodornase (streptococcal deoxyribonuclease) depolymerizes DNA. The enzymatic activity can be measured by the decrease in viscosity of known DNA solutions.
Hyaluronidase
Hyaluronidase splits hyaluronic acid, an important component of the ground substance of connective tissue. Thus, hyaluronidase aids in spreading infecting microorganisms (spreading factor). Hyaluronidases are antigenic and specific for each bacterial or tissue source.
Pyrogenic Exotoxins (Erythrogenic Toxin)
Pyrogenic exotoxins are elaborated by S pyogenes. There are three antigenically distinct streptococcal pyrogenic exotoxins: A, B, and C. Exotoxin A has been most widely studied. It is produced by group A streptococci that carry a lysogenic phage. The streptococcal pyrogenic exotoxins have been associated with streptococcal toxic shock syndrome and scarlet fever. The pyrogenic exotoxins act as superantigens, which stimulate T cells .
Diphosphopyridine Nucleotidase
This enzyme is elaborated into the environment by some streptococci. This substance may be related to the organism s ability to kill leukocytes. Proteinases and amylase are produced by some strains.
Hemolysins
The beta-hemolytic group A S pyogenes elaborates two hemolysins (streptolysins). Streptolysin O is a protein (MW 60,000) that is hemolytically active in the reduced state (available –SH groups) but rapidly inactivated in the presence of oxygen. an antibody that appears in humans following infection with any streptococci that produce streptolysin O. This antibody blocks hemolysis by streptolysin O. This phenomenon forms the basis of a quantitative test for the antibody. An antistreptolysin O (ASO) serum titer in excess of 160–200 units is considered abnormally high and suggests either recent infection with S pyogenes or persistently high antibody levels due to an exaggerated immune response to an earlier exposure in a hypersensitive person. Streptolysin S is the agent responsible for the hemolytic zones around streptococcal colonies growing on the surface of blood agar plates. It is elaborated in the presence of serum—hence the name streptolysin S. It is not antigenic,
Pathogenesis & Clinical Findings
A Streptococci
The portal of entry determines the principal clinical picture. In each case, however, there is a diffuse and rapidly spreading infection that involves the tissues and extends along lymphatic pathways with only minimal local suppuration. From the lymphatics, the infection can extend to the bloodstream.
1-Erysipelas 2- Cellulitis 3-Necrotizing Fasciitis (Streptococcal Gangrene) 4- Puerperal Fever 5-Bacteremia/Sepsis
Diseases Attributable to Local Infection with S pyogenes and Their By-Products
1-Streptococcal Sore Throat 2-Streptococcal Pyoderma
3-Streptococcal Toxic Shock Syndrome, and Scarlet Fever
Poststreptococcal Diseases (Rheumatic Fever, Glomerulonephritis)
Following an acute S. pyogenes infection, there is a latent period of 1–4 weeks, after which nephritis or rheumatic fever occasionally develops. Nephritis is more commonly preceded by infection of the skin; rheumatic fever is more commonly preceded by infection of the respiratory tract.
Acute Glomerulonephritis
This sometimes develops 3 weeks after S pyogenes skin infection (pyoderma, impetigo). Glomerulonephritis may be initiated by antigen-antibody complexes on the glomerular basement membrane..
Rheumatic Fever
This is the most serious sequela of S pyogenes because it results in damage to heart muscle and valves
Rheumatic fever has a marked tendency to be reactivated by recurrent streptococcal infections, whereas nephritis does not. The first attack of rheumatic fever usually produces only slight cardiac damage, which, however, increases with each subsequent attack. It is therefore important to protect such patients from recurrent S pyogenes infections by prophylactic penicillin administration
Immunity
Anti-M type-specific antibodies can be demonstrated in a test that exploits the fact that streptococci are rapidly killed after phagocytosis. Antibody to streptolysin O develops following infection.
Treatment
All S pyogenes are susceptible to penicillin G, and most are susceptible to erythromycin. Some are resistant to tetracyclines. Antimicrobial drugs have no effect on established glomerulonephritis and rheumatic fever.

Epidemiology, Prevention, & Control
Control procedures are directed mainly at the human source:

   (1) Detection and early antimicrobial therapy of respiratory and skin infections with group A streptococci. (2) Antistreptococcal chemoprophylaxis in persons who have suffered an attack of rheumatic fever.
(3) Eradication of S pyogenes from carriers. This is especially important when carriers are in areas such as obstetric delivery rooms, operating rooms, classrooms, or nurseries