Virulence factors of Group-A Streptococcus

• 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.

E) Exotoxins

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.

F) Haemolysin

• 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.

i) Streptokinase(fibrinolysin)

• 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.

iv) Hyaluronidase

• 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.

References: 

i) https://www.uptodate.com/contents/group-a-streptococcus-virulence-factors-and-pathogenic-mechanisms

ii) https://microbeonline.com/virulence-factors-streptococcus-pyogenes-roles/

Virulence factors of Group-A Streptococcus