Gram Positive Cocci

Question 1

*Streptococcus pyogenes *Gen Characteristics

Answer 1

Group A Strep

• Gram positive coccus
• Catalase negative
• Beta-hemolytic
• Bacitracin sensitive
• Facultative anaerobe
• Grows in chains
• Encapsulated
• part of the normal flora of skin and the oropharynx

Question 2

S. pyogenes toxins

Answer 2

• Streptococcal exotoxins A, B, & C = superantigens → bridge TCR and MHC → activation of many **polyclonal **T cells → Streptococcal TSS (esp. A) or Scarlet Fever
• Streptolysin O (SLO): binds cholesterol and forms pores in membranes → release of phagocyte lytic enzymes, nitrogen radicals → tissue injury and ⇡inflammation
• Streptokinase: converts plasminogen → plasmin → lysis of fibrin clots and ECM → promotes systemic invasion
• Hyaluronidase: breaks down connective tissue
• C5a peptidase: inactivates C5a → prevents neutrophil chemoattraction
• M proteins: antiphagocytic protein in the cell wall that blocks binding of C3b → prevents opsonization and phagocytosis
• DNase: digests DNA

Question 3

S. pyogenes capsule

Answer 3

Consists of hyaluronic acid, which is a normal constituent of the human ECM (i.e., molecular mimicry) → prevents opsonization by host antibodies → capsule is not immunogenic ∴ a capsular vaccine cannot be developed

Question 4

S. aureus toxins

Answer 4

• Cytolytic (Alpha, beta, delta, & gamma) toxins:
  
  • Alpha toxin = channel-forming toxin that uses a beta-barrel structure → lysis of RBCs/WBCs/endothelial cells
  • PVL (leukocidin) =
    
    • found most frequently in CA-PNA
  • Staphylokinase (Sak): converts plasminogen → plasmin → lysis of fibrin clots → facilitates escape of S. aureus from local site of infection
• Superantigens: bind outside peptide-binding cleft of MHC and bridge MHC w/ TCR → 10-fold polyclonal proliferation of T cells
  
  • Toxic Shock Syndrome Toxin-1 (TSST-1): causes TSS
  • Staphylococcal enterotoxin (SE): causes food poisoning

Question 5

Streptococcus pneumoniae Gen Characteristics

Answer 5

• Gram positive coccus
• Catalase negative
• Alpha-hemolytic
• Optochin susceptible
• Bile-esculin negative
• Quellung positive
• Encapsulated
• Grows in pairs (diplococci)

Question 6

S. aureus toxins that disable the immune system

Answer 6

• <!--StartFragment-->Protein A = an antiphagocytic factor that binds the Fc portion of IgG molecules leaving the antigen-binding Fab region directed externally (turned around away from the S. aureus)
  • Protects the microorganism from opsonization and phagocytosis
• α-toxin inserts in lipid bilayer to form transmembrane pores → lysis of cytoplasmic membranes → egress of vital molecules → cell death
  
  • Not secreted by CoNS
• Coagulase activates prothrombin w/o the usual proteolytic cleavages to form a fibrin clot
  
  • Forms fibrin coat around the organism → protects the organism from phagocytosis
• Leukocidins destroy WBCs
  
  • CA-MRSA produce Panton-Valentine Leukocidin (PVL), which is associated with a propensity to form abscesses

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Question 7

S. aureus toxins that disable antibiotics

Answer 7

• Penicillinase = secreted form of β-lactamase, which disrupts the β-lactam portion of penicillins and inactivates them, which is why it is mostly penicillin resistant
• Novel penicillin binding protein/transpeptidase = enzyme necessary for peptidoglycan formation that penicillin inhibits. If they have new one that penicillin can’t target, this makes it resistant to penicillinase-resistant penicillins and cephalosporins

Question 8

S. aureus toxins that tunnel through host tissue

Answer 8

• <!--StartFragment-->Hyaluronidase breaks down proteoglycans in host connective tissue
• Staphylokinase similar to streptokinase, it lyses formed fibrin clots
• Lipase degrades fats and oils that accumulate on the surfaces of our body
  
  • Helps S. aureus’s colonization of the sebaceous glands
• Protease destroys tissue proteins

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Question 9

S. aureus exotoxins

Answer 9

• <!--StartFragment-->Exfolatin binds to stratum granulosum in skin → disruptions in intercellular junctions → intercellular splitting of the epidermis between the stratum spinosum and stratum granulosum
  • Causes the skin to slough off → blisters (bullous impetigo) and Scalded Skin Syndrome (esp. in newborns)
• TSST-1 and other superantigen (SAgs) toxins
  
  • SAgs bind MHCII molecules without being processed by an APC first
  • They are also strongly mitogenic for T cells
  • This process bypasses antigen-processing specificity and leads to massive cytokine release (TNF and IL-1) → TSS with the following CP:
    
    • Sudden onset of high fever
    • Nausea, vomiting, & watery diarrhea
    • Diffuse erythematous rash (follows a few days later)
    • Desquamation of palms and soles (occurs late in the course of illness)
    • Septic shock
• Heat stable Enterotoxins → Gastroenteritis (food poisoning, vomiting, & diarrhea)
  
  • retain activity even after boiling or exposure to low pH
  • Stimulate reflexes in the abdominal viscera → sent to medullary emetic centers via vagus n. → vomiting

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