Pathogenesis of Streptococci Flashcards
How are Streptococci Identified?
Through lancefield grouping
List the different groups of strep with an example, area of infection and disease caused
Group A: S pyogenes, Skin/throat, many
Group B: S algalactiae, Female GT/GIT, Neonatal meningitis
Group D: Enterococcus, Oral/GIT/Female GT, UTI/endocarditis
What form of haemolysis is Group A strep? what are some characteristics
B Haemolytic
Pyogenic (pus forming)
Sensitive to bacitracin
What are 2 examples of respiratory infections and skin infections caused by Strep
Respiratory infections:
Acute pharyngitis (strep throat)
Scarlet fever
Skin infections: Impetigo Erysipelas Cellulitis necrotising fascilitis Toxic shock syndrome Acute rheumatic fever
Explain sequelae of skin or throat infections with strep
Acute glomerulonephritis may occur which may result in kidney failure
Explain what hyaluronic acid capsules are and their purpose (strep)
- causes bacteria to look mucoid in appeatance
- varies slightly strain to strain
- anti-phagocytic properties (interference with the interaction of bound C3b complement with phagocytes, non-immunogenic)
How are M-proteins able to bind to many mammalian proteins (strep)
- Fibrogen (adhesion by forming complex to adhere to platelet
- Serum albumin (masking of bacteria, bacteria looks like host protein, able to bind to Fc region of IgG)
- Factor H (regulatory protein for alternative complement pathway, complement C3b mediator and degrades it, prevents completion of complement cascade)
What does an M-protein look like under an electron micrograph (strep)
Appears as har like structures
What are the 3 regions of M-proteins (strep)
- A repeat (high variability)
- B repeat (High variability)
- C repeat (Highly conserved)
How many M-protein sero-types are there? How are they defined (strep)
- > 80
- Based on difference in A and B regions
Not all M proteins exhibit the same function, which M proteins bind fibronectin and which do not? (strep)
- M3 binds fibronectin
- M5 and M24 do not bind Fibronectin
What gene encodes M proteins (strep)
- Emm genes
How many bp and amino acid residues are in M1? (strep)
- 1452 bp
- 482 amino acid residues
Explain the gene structure of M proteins (strep)
- 1-3 emm proteins in tandem
- 4 subfamilies (SF1-SF4) with 3’ end conserved
- 5 pattern (A-E) (content and arrangement)
- Serotype determinant (5’ end variable region, Emm types >150)
What are the 3 steps in basic mechanisms of pathogenesis (strep)
- Invade and spread through tissue
- Production of toxins
- Provoke an autoimmune response
Explain how Strep invades tissue
- bind to extracellular matric components or specific receptors
- M protein attaches to keratinocytes in skin infection, delete C1 and C2 repeats, membrane cofactor protein CD46 is the receptor for M protein
- Many other adhesions
Explain how strep evades phagocytic cells
- evades recognision through proteases
- protect strep from interacting with phagocytic cells by using C5a peptidase (serine protease which degrades C5a, a complement component that recruits and activates phagocytic cells)
How does Strep spread in tissue?
- secrete digestive enzymes
- Pus from strep is thin and runny because DNA and gibrin are degraded
- Streptokinase activates protein plasminogen to plasmin which dissolves fibrin clots. 2 types (SLO and SLS), SLO is oxygen sensitive and enhances haemolysis under anaerobic conditions, SLS is oxygen stable and is non immunogenic
What are the hallmarks of toxin mediated disease?
- Damage at sites distinct from primary site of infection
How can strep produce toxin mediated disease?
- exotoxins (Strep pyrogenic exotocins SPE, Spe A-J excluding D,E,I)
- superantigens stimulate T cell proliferation (up to 20%)
- also induce release of cytokines leading to inflammation and septic shock
- responsible for the rash in scarlet fever as it has a direct effect on the capillary bed
What are the hallmarks of autoimmune based disease
- unrelated disease post infection e.g. rheumatic fever
How can strep produce autoimmune based disease?
- antigenic mimicry (strep antigens hsare epitopes with human tissues, antibodies cross react with host tissue leading to damage)
Explain autoimmunity and molecular mimicry in regards to rheumatic fever (strep)
- autoantibodies against the heart is associated with rheumatic fever
- Monoclonal antibodies identifies myosin as the autoantigen in the heard
- M protein antibodies cross react with myosin: M5, M6
Explain molecular mimicry in glomerulonepghritis (strep)
- less certain of its role
- glomerular basement membrane shares antigen with M12 protein
- Mab against glomeruli reacted with M12 protein
