0505 - Staph Aureus and Virulence Factors Flashcards
What does it mean to be coagulase positive? (clinically and microbiologically)
The ability to catalyse the conversion of fibrinogen to fibrin in the body. Microbiologically, form clumps on slide or in tube to test.
Coagulase is an important invasin and impedin, allows it to form a clot, evade phagocytosis, and then use staphylokinase to break the clot down and continue invading.
What is the role of DNase? (Clinically and microbiologically)
Degrades DNA in tissue. In lab, DNase clears an area around colony. S. Aureus only one that’s both coagulase and DNase positive.
How does staph aureus differ from coagulase negative staph species?
Number of toxins =>30 vs None
Number of adhesins = >20 vs Less than 10
Staph Aureus only one that produces both coagulase and DNase.
What is an Adhesin
Coordinates binding of the organism to host tissue
What is an Invasin
Enable organism to invade host cell
What is an Impedin
Enable organism to evade some host defence mechanisms
What is an Aggresin
Causes direct damage to the host
What is a Modulin
Induces indirect damage to the host (e.g. antigen-antibody complexes).
How are Staph Aureus virulence factors categorised
Genetic component and product.
Regulatory systems - Accessory Gene regulator (agr complex) - influences production of downstream virulence factors
Cell surface - adhesins (lots of binding proteins)
Secreted enzymes and proteins
Toxins and haemolysins
Small colony variants - tailored for small colonies, may allow survival in colonisation.
What are some cell surface determinants of Staph Aureus virulence?
LOTS - mostly adhesins
Capsule - impedin to resist phagocytosis
Surface adhesins - Clumping factors A and B (coagulase), fibronectin/colllagen/elastin binding proteins
Teichoic and Lipoteichoic acid
Peptidoglycan
Ability to form biofilms - (e.g. on prosthetics) - KEY
What are some enzymes/proteins secreted by staph aureus
All are responsible for tissue damage and invasion.
Coagulase (also impedin)
Phospholipase C - damage RBCs
Staphylokinase (also impedin)
What are the toxins and haemolysins of Staph aureus?
These are Aggresins - most important virulence factors
Haemolysins
Leucocidins (lyse WBCs)
Exfoliative toxins - damage skin and subcut tissue
Superantigen toxins - very important - aggressins and impedins, can cause auto-immune diseases. TSST-1 and Enterotoxins.
Phenol soluble modulins.
What are the Staph Aureus Haemolysins?
Pore-forming toxins that lyse RBCs and other cells. Alpha haemolysin is most commonly secreted, causes skin and soft tissue infections (SSTI), and pneumonia.
What are the Leucocidins of Staph aureus?
Bi-component toxins - come together on cell surface to form a pore.
Panton-Valentine Leucocidin (PVL) is implicated in many infections, but only present in 5% of isolates. Responsible to severe soft tissue infections and pneumonias. 85% of community associated MRSA has this toxin.
What Staph Aureus toxins are associated with Staphylococcal scalded skin syndrome?
Exfoliative toxins A and B. They directly break down the stratum granulosum.
What are the two types of superantigen possessed by Staph Aureus?
(KEY EXAM CONCEPT)
TSST-1 - Toxic Shock Syndrome Producing Toxin - associated with menstrual TSS
Staph Enterotoxins - cause food poisoning.
How to Staph superantigen toxins work?
KEY EXAM CONCEPT
Don’t follow normal path of other antigens - activate T-cells non-specifically (20% T-cells activated, normally 0.0001% activated by infeciton).
Leads to cytokine storm and overwhelming inflammatory response. This results in endothelial leakage, haemodynamic shock, multi-organ failure and possibly death.
How does Staph Aureus evade the immune system?
Inhibit leukocyte migration and phagocytosis
Prevent Opsonin coating via capsule - Ig binding and opsonisation blocked
Protein A and Staphylokinase are peptides that destroy Ig’s
Complement is evaded by capsular polysaccharides, staphylokinase and protein surfaces.
Antimicrobial peptides - staphylokinase, aureolysin, to provide positive environment.
What role does the agr gene regulator play in Staph Aureus infection?
agr plays a role in quorum sensing, and expression of key virulence factors.
When agr activated, adhesins decrease, toxins increase, and vice versa. So colonising strains (with more adhesins) are less likely to produce virulence factors and invade.
agr=infection.
How can Staph Disease present?
Pyogenic/Invasive and toxin mediated
Invasive - Actual infections and most inflammation - particularly skin and soft tissue and bacteraemia and associated internal infection. Often linked with healthcare facilities.
Toxin mediated - toxic shock syndrome, staph scalded skin syndrome, food poisoning.
What are the Skin and soft tissue infections caused by staph?
Epidermis - Impetigo
Superficial dermis - Folliculitis
Deep dermis - furuncle or carbuncle
Subcutaneous infection - cellulitis, fasciitis
Staphylococcal scalded skin syndrome (actually toxin-mediated)
Briefly outline Staph Bloodstream infections
Mostly healthcare associated
20-30% mortality rate
1/3 develop metastatic complications, particularly infective endocarditis. Unlike strep, staph can actually damage the valve and form vegetations on an otherwise undamaged valve.
Briefly outline Staph bone and joint infections
Osteomyelitis - 50-70% staph aureus.
Often diabetic foot infections or foot trauma in kids.
Prosthetic joint infections - can be acute or delayed (12 week post-surgery divid). CoNS most common, then staph aureus.
Small colony variants implicated as cause of persistant bone infections and refractory to treatment.
Briefly outline Staph toxin-mediated diseases
Staph food poisoning - ingestion of pre-formed toxins (not live staph) in food/drink. Symptoms 2-6 hours after ingestion. 10% require hospitalisation.
Toxic shock syndrome - potentially leading to death.
Staphylococcal scalded skin syndrome.
What are the characteristics of healthcare associated MRSA?
Resistant to >3 classes AND beta lactams
Highly clonal
What are the characteristics of community-associated MRSA?
Resistant to less than 3 classes and beta lactams
Polyclonal generally
How is staph able to obtain antibiotic resistance?
Predominantly based on altered penicillin binding protein 2a (PBP2a) - mecA gene.
If damaged, penicillin can’t bind and can’t bind. MecA carried on Staphylococcal chromosome cassette (SCC).
