- Streptococcus are gram positive, catalase negative cocci.
- Are spherical or ovoid, 0.5-1µ in diameter, arranged in chains, non-motile and non-sporing.
- They may become gram negative in ageing culture when the bacteria die.
- Some of the strains possess capsules made up of hyaluronic acid while some of the strains possess capsules composed of polysaccharide.
- Human beings are affected by a large number of Streptococci which are divided into various groups.
- But mostly hemolytic Streptococci which are pathogenic fall into group A.
- These are called Streptococcus pyogenes.
- The various virulence factors of Group A Streptococcus are as follows:
A) Capsular hyaluronic acid
- In group A and C Streptococci, hyaluronate capsule may be present during logarithmic phase of growth.
- This hyaluronate gets destroyed due to production of hyaluronidase during stationary phase.
- Capsule may induce antibody which is not protective.
- It is not immunogenic but protects the cells from phagocytosis.
B) Group specific polysaccharide antigen
- Group polysaccharide plays an important pathogenic role in the non-suppurative sequelae of streptococcal infection.
- Cell wall of Streptococcus pyogenes is made up of an outer layer of protein (fimbria containing protein) and lipoteichoic acid, middle layer of group-specific carbohydrate and an inner layer of peptidoglycan.
- These molecules are chemically similar in structure to human tissue antigens, particularly those of heart, kidney and joints.
- As a result, immune response directed against S. pyogenes may become auto-reactive and contribute in the pathogenesis of endocarditis, glomerulonephritis or arthritis.
C) Type specific protein antigen
i) M protein
- It is distributed throughout the surface along with the fimbriae.
- It is acid and heat resistant, susceptible to tryptic digestion and soluble in alcohol.
- It resists phagocytosis, helps in adherence of the organism to the host epithelial cells.
- Thus, it helps by enhancing the virulence of organism.
- In absence of M protein, Streptococci are avirulent and it can be extracted by application of heat.
ii) T and R proteins
- They do not have any role in virulence.
- T antigens include a number of immunologically distinct proteins.
- They are present in many serotypes of S. pyogenes.
- They are not distributed parallel with M proteins.
- M types share the same of T substance.
- Another surface protein R has been found in some types of S. pyogenes and in some strains of groups B, C and G.
D) Other cell surface proteins
- Protein F (fibronectin-binding protein) has a receptor of fibronectin, a matrix protein on eukaryotic cells, which acts as major adhesin to bind to pharyngeal epithelial cells.
- Protein G prevents the effective phagocytosis by binding with IgG through the Fc region and hindering antibody binding.
i) Erythrogenic toxins
- Lysogenized strains of group-A Streptococci mostly produce these toxins.
- It is antigenic and is neutralized by convalescent sera.
- It acts directly on hypothalamus and cause pyrogenecity.
- They cause the characteristic rash of scarlet fever.
- But, the mechanism of the action of this toxin is not clear.
ii) Exotoxin A
- It is closely related to erythrogenic toxin and to some extent to TSST1 of S. aureus.
- It is a super antigen which is responsible for the systemic manifestations of group-A streptococcal infection.
- It is found in about 50% of group-A streptococci.
iii) Exotoxin B
- It is a cysteine protease and responsible for tissue destruction in patients with necrotizing fasciitis.
iv) Cardio-hepatic toxin
- It is responsible for heart and liver failure.
- Haemolysin S and O are produced by most groups of group-A streptococci and some by group C and G.
- These are also known as haemolysins.
i) Streptolysin O
- It is proteinous molecule having molecular weight of 60,000.
- In reduced state, it works as haemolytic which can cause complete haemolysis around the colony.
- It is oxygen liable thus named so.
- It is immunogenic and demonstrable only in deep colonies.
- It binds to the cholesterol containing cell membranes thus causing lysis of red cells and produces holes in it.
- It is cytotoxic for neutrophils, platelets and cardiac tissue.
- Against this antigen, antistreptolysin O appears in the sera of humans following streptococcal infection.
- Antistreptolysin O blocks the haemolysis by streptolysin O by which the quantitative estimation of the antibody can be done.
ii) Streptolysin S
- It is an oxygen stable haemolysin which haemolyse surface colony.
- It also shows leukocidal action in addition to haemolytic property.
- It is not antigenic though it is proteinous in nature.
G) Spreading factors (enzymes)
- Streptokinase, de-oxyribonuclease and hyaluronidase may be produced by some strains of group A streptococci and some by group C and G.
- It promotes the lysis of human blood clot by catalyzing the conversion of plasminogen (plasma precursor) into plasmin.
- Streptokinase A and B have been detected.
- It is immunogenic and in serum of the patient’s, neutralizing antibodies (antistreptokinase) appears by which retrospective streptococcal infection can be studied.
- It prevents the formation of effective fibrin barrier around the lesion by which it can easily spread during the infection time.
ii) Streptococcal de-oxyribonuclease
- A, B, C and D are the types of de-oxyribonucleases that are responsible in degrading DNA.
- These enzymes can easily liquefy the highly viscous DNA that accumulates in thick pus derived from the disintegrated poly-morphonuclear leucocytes.
- It helps in explaining the thin serous character of streptococcal exudate.
iii) Nicotinamide adenine dinucleotidase (NADase)
- It helps in liberation of nicotinamide molecules by acting on the co-enzyme DPN (di-phosphopyridine nucleotide).
- It is antigenic in nature and may be leukotoxic.
- Hyaluronic acid gets splitted from ground substance of connective tissues.
- This helps in spreading of streptococcal lesion along intercellular spaces.
- It is antigenic.
v) Lipoproteinase (serum opacity factor)
- Opalescence of the serum can be produced if certain M types of group A streptococci grown in horse serum broth.
- The opacity factor is lipoproteinase and antigenic in nature.
vi) Other extracellular products
- Various enzymes are produced by other members like DPNase, neuraminidase, phosphatase, esterase, amylase, N-acetyl glucosaminidase, lipase, beta-glucoronidase which are harmful to tissues.
Virulence factors of Group-A Streptococcus