More about strep classifications re: virulence, toxins, etc

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Streptococcal Infection

Author(s): Bashir Gaash

Streptococci were first demonstrated in patients with erysipelas by

Billroth in 1874, and isolated in 1883 by Fehleisen, but it was

Rosenbach who, in 1884, applied the designation to the group. The

name `streptococcus' is derived from the Greek `streptos' signifying

a chain formed of links or a necklace of beads; `coccus' meaning a

berry.

The organisms may occur in pairs or in chains of varying length.

There are two main types: haemolytic & non-haemolytic. The

haemolytic ones are further divided on whether they lead to alpha,

beta or gamma hemolysis. In beta-haemolysis, a colony of organisms

grown on blood agar is surrounded by a clear zone, 2-4 mm in

diameter, within which the RBC are completely lysed.

Strep. pyogenes and other streptococci that show a similar phenotype

are called â-haemolytic streptococci. They are pathogenic in man. In

contrast, species that are typically part of the normal throat flora

are either non-haemolytic, or they produce á-haemolysis,

characterized by a zone of incomplete, often greenish clearing

around colonies grown on blood agar.

The â-hemolytic streptococci grow poorly on ordinary nutrient agar

but more readily on blood agar: the zones of beta-hemolysis are

fully developed after 18 hours' growth and very little enlargement

occurs thereafter. The colonies do not exceed 1 mm in size. Although

the organisms grow both aerobically & anaerobically, â-haemolysis

develops more readily anaerobically. Although the growth is possible

over a wider range of temperatures, the optimum temperature is 37°C.

Virulence Factors & Toxins

a) Extracellular products:

Haemolysins (Streptolysins): Two types of haemolysins, O & S, which

are at peak 8 hours after incubation at 37°C, are produced in broth

culture. The O-haemolysin is readily oxidized (derives its name from

oxygen-liability) while the S-hemolysin is oxygen-stable, (derives

its S from being produced by streptococci growing in the presence of

serum). The former is produced by all streptococci while as the

latter is only produced by group A, C & G.

Streptolysin O & S are the proteins responsible for beta-haemolysis.

They lyse RBC & WBC by making holes in their cell membrane.

Streptolysins are toxic to the body; streptolysin O is antigenic and

leads to production of antibodies (antistreptolysin O) while

streptolysin S is either non-antigenic or too weakly antigenic.

Antistreptolysin O (ASO) is a true antibody which rises as a result

of streptococcal infection. That is why practitioners want to know

its titre. It is an exceedingly useful indicator of recent

streptococcal infection.

Anti-streptolysin `O' is toxic to a variety of cells and cell

fractions including polymorphonuclear leukocytes, platelets,

lysosomes etc. Previously it was thought that a separate

haemolysin , leucocidin, destroyed white blood cells. Now we know

that it is identical with streptolysin O.

Several extracellular factors serve to facilitate liquefaction of

pus and the spreading of streptococci through tissue planes. Four

antigenically different DNAses (A, B, C & D) participate in the

degradation of deoxyribonucleic acid. Previously, de-oxyribonuclease

used to be called Streptodornase. Streptokinase, another toxic

product of GAS, leads to dissolution of clots by catalyzing the

conversion of plasminogen into plasmin. Proteinase is another factor

liberated by GAS. A spreading factor, hyaluronidase, is also found

in streptococcal filtrates. These enzymes degrade the tissue and

enhance the spread of infection. The tissue destruction in turn

leads to inflammatory response which leads to various symptoms and

signs.

Streptococcal pyrogenic exotoxins (SPEs) are a family of genetically

similar exotoxins that cause severe streptococcal disease unrelated

to strep throat. These diseases include scarlet fever, streptococcal

toxic shock syndrome, and `flesh eating' necrotizing fasciitis.

These exotoxins are superantigens, which can lead to massive

activation of T cells. The resulting uncontrolled release of

cytokines is responsible for the seriousness of these infections.

Erythrogenic (Dick) toxin belongs to this group. It is an SPE

released from the infection site which enters the bloodstream,

circulates throughout the body and leads to a redness of skin and

whitish coating of the tongue.

Antibodies to five of extracellular products are used in the

serodiagnosis of streptococcal infection. These are ASO, anti-DNase,

antihyaluronidase, antinicotinamine adenine dinucleotidase, and

antistreptokinase.

Somatic Antigens:

In addition to elaborating various toxins, Group A streptococci

(GAS) posses different somatic protein antigens, which enable GAS to

be further divided. This typing is of great value in the study of

outbreaks of streptococcal infection. M protein causes the

degradation of complement component C3b, an opsonin that would

otherwise promote phagocytosis of the bacteria. M protein is

essential for the virulence of GAS, because antibody to it prevents

infection from occurring. Organisms which do not have M protein are

avirulent. More than 90 different kinds of M protein exist and,

unfortunately, antibody to one type does not prevent infection by a

strain that has another kind of M protein.

Another protein antigen closely related to the M protein is the

serum opacity-factor (OF). This is itself antigenic and type-

specfic; it is useful as an epidemiological marker in typifying GAS

when they are not identifiable on the basis of M antigen. It has

been found that immune response to M-protein is generally weaker

after pharyngeal infection with OF-positive than with OF-negative

strains.

Protein F of the cell wall mediates attachments of GAS to the throat

by adhering to a protein found on the surface of the epitheloid

cells. Another cell wall constituent, lipoteichoic acid, plays a

similar role in the first step in colonization ie adherence of GAS

to fibronectin on the surface of human epithelial cells.

Protein G of the bacterium binds to the Fc segment of immunoglobulin

G. The effect is to prevent phagocytosis mediated by specific

antibody against the bacterium. There are other multifunctional

surface proteins which have the ability to bind to host proteins,

including immunonoglobulin G & A.

C5a peptidase is an enzyme released by GAS, which destroys the C5a

component of the complement system, which normally attracts

phagocytes to the site of a bacterial infection. This cell-bound

peptidase cleaves the C5a component of the complement and inhibits

neutrophil chemotaxis.

Both, M antigen and the capsule, which contains mucopolysaccharide

hyaluronic acid, are related to the virulence of the strain. M

protein is the major somatic virulence factor, while hyaluronic acid

capsule is an accessory virulence factor. Both retard phagocytosis

of the microorganism by polymorphonuclear leukocytes's and strains

containing this, being resistant to phagocytosis, multiply rapidly

in body and initiate disease.