Streptococcus

Streptococcus
Introduction
The streptococci are gram-positive spherical bacteria that characteristically form pairs or chains during growth. They are widely distributed in nature. Some are members of the normal human flora others are associated with important human diseases. Streptococci elaborate a variety of extracellular substances and enzymes. The streptococci are a large and heterogeneous group of bacteria and understanding the classification of it is a key to understanding their medical importance.
Classification of Streptococci
The classification of streptococci into major categories has been based on a series of observations over many years: (1) colony morphology and hemolytic reactions on blood agar (2) serologic specificity of the cell wall group-specific substance and other cell wall or capsular antigens (3) biochemical reactions and resistance to physical and chemical factors and (4) ecologic features. Molecular genetics have also been used to study the streptococci. Combinations of the above methods have permitted the classification of streptococci for purposes of clinical and epidemiologic convenience.


Table 1. Characteristics of Medically Important Streptococci.



Name Group-Specific Substance1
  Hemolysis2
  Habitat Important Laboratory Criteria Common and Important Diseases
Streptococcus pyogenes  A Beta Throat, skin Large colonies (> 0.5 mm), PYR3 test positive, inhibited by bacitracin
  Pharyngitis, impetigo, rheumatic fever, glomerulonephritis
Streptococcus agalactiae  B Beta Female genital tract Hippurate hydrolysis, CAMP-positive4
  Neonatal sepsis and meningitis
Streptococcus dysgalactiae subspecies equisimilis; others   C, G Beta (human) infections), alpha, none Throat Large (> 0.5 mm) colonies Pharyngitis, pyogenic infections similar to group A streptococci
Enterococcus faecalis (and other enterococci)  D None, alpha Colon Growth in presence of bile, hydrolyze esculin, growth in 6.5% NaCl, PYR-positive Abdominal abscess, urinary tract infection, endocarditis
Streptococcus bovis (non-enterococcus)   D None Colon Growth in presence of bile, hydrolyze esculin, no growth in 6.5% NaCl, degrades starch Endocarditis, common blood isolate in colon cancer
Streptococcus anginosus group (S anginosus, S intermedius, S constellatus, S milleri group)  F (A, C, G) and untypable Alpha, beta, none Throat, colon, female genital tract Small (< 0.5 mm) colony variants of beta-hemolytic species. Group A are bacitracin-resistant and PYR-negative. Carbohydrate fermentation patterns Pyogenic infections, including brain abscesses
Viridans streptococci (many species) Usually not typed or untypable Alpha, none Mouth, throat, colon, female genital tract Optochin-resistant. Colonies not soluble in bile. Carbohydrate fermentation patterns Dental caries (S mutans), endocarditis, abscesses (with many other bacterial species) 
Streptococcus pneumoniae  None Alpha Throat Susceptible to optochin. Colonies soluble in bile, quellung reaction-positive Pneumonia, meningitis, endocarditis
Peptostreptococcus (many species) None None, alpha Mouth, colon, female genital tract Obligate anaerobes Abscesses (with multiple other bacterial species)


1Lancefield classification.

2Hemolysis observed on 5% sheep blood agar after overnight incubation.
3Hydrolysis of L-pyrrolidonyl-2-naphthylamide ("PYR").
4Christie, Atkins, Munch-Peterson test. CAMP test is done to detect the production by group B but not other Streptococci, of a diffusible extracellular protein (CAMP factor) that acts synergistically with the ?-lysin produced by Staphylococcus aureus to cause enhanced lysis of red blood cells on blood agar.
Hemolysis
Many streptococci are able to hemolyze red blood cells in vitro in varying degrees. Complete disruption of erythrocytes with clearing of the blood around the bacterial growth is called beta hemolysis. Incomplete lysis of erythrocytes with reduction of hemoglobin and the formation of green pigment is called alpha hemolysis. Other streptococci are non-hemolytic (sometimes called gamma hemolysis).

Hemolyses of Streptococcus spp.
(left) ?-hemolysis (S. mitis);
(middle) ?-hemolysis (S. pyogenes);
(right) ?-hemolysis (= non-hemolytic, S. salivarius)
Group-Specific Substance (Lancefield Classification)
This carbohydrate is contained in the cell wall of many streptococci and forms the basis of serologic grouping into Lancefield groups A–H and K–U. The serologic specificity of the group-specific carbohydrate is determined by an amino sugar. For group A streptococci, this is rhamnose-N-acetylglucosamine; for group B, it is rhamnose-glucosamine polysaccharide; for group C, it is rhamnose-N-acetylgalactosamine; for group D, it is glycerol teichoic acid containing D-alanine and glucose; and for group F, it is glucopyranosyl-N-acetylgalactosamine.
Capsular Polysaccharides
The antigenic specificity of the capsular polysaccharides is used to classify S pneumoniae into over 90 types and to type the group B streptococci (S agalactiae).
Biochemical Reactions
Biochemical tests include sugar fermentation reactions, tests for the presence of enzymes, and tests for susceptibility or resistance to certain chemical agents. Biochemical tests are most often used to classify streptococci after the colony growth and hemolytic characteristics have been observed.
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


Viridans Streptococci
The viridans streptococci include S mitis, S mutans, S salivarius, S sanguis, and others. Typically they are alpha -hemolytic, but they may be nonhemolytic. Their growth is not inhibited by Optochin, and colonies are not soluble in bile (deoxycholate). The viridans streptococci are the most prevalent members of the normal flora of the upper respiratory tract and are important for the healthy state of the mucous membranes .They may reach the bloodstream as a result of trauma and are a principal cause of endocarditis on abnormal heart valves. Some viridans streptococci (eg, S mutans) synthesize large polysaccharides such as dextrans or levans from sucrose and contribute importantly to the genesis of dental caries.
In the course of bacteremia, viridans streptococci, pneumococci, or enterococci may settle on normal or previously deformed heart valves, producing acute endocarditis. Subacute endocarditis .

Nutritionally Variant Streptococci
The nutritionally variant streptococci, previously S defectives and S adjacens and additional species, are now classified in the genus Abiotrophia and the genus Granulicatella. They have also been known as "nutritionally deficient streptococci" and "pyridoxal-dependent streptococci." They require pyridoxal or cysteine for growth on blood agar or grow as satellite colonies around colonies of staphylococci and other bacteria.

Peptostreptococcus (Many Species)
These streptococci grow only under anaerobic or microaerophilic conditions and variably produce hemolysins. They are part of the normal flora of the mouth, upper respiratory tract, bowel, and female genital tract. They often participate with many other bacterial species in mixed anaerobic infections. Such infections may occur in wounds, in the breast, in postpartum endometritis, following rupture of an abdominal viscus, the brain, or in chronic suppuration of the lung. The pus usually has a foul odor.