Week 2: Staphylococcal diseases/infections

Question 1

Staphylococcus aureus

Answer 1

• Gram Positive coccoid bacterium
• Produces coagulase
• Common human commensal, versatile + highly adaptable
• Can be found in human skin, specifically anterior nares

Question 2

Some S. aureus diseases

Answer 2

+ Boils + pimples
+ Impeligo
+ Cellulitis
+ Osteomyelitis
+ Meningitis
+ Endocarditis
+ Infection of prostheses
+ Toxic shock syndrome
Abscesses are common within many of these diseases

Question 3

Modifiying the cell membrane for antimicrobial peptide resistance

Answer 3

• Modifications can be made by:
  + D-alanine teichoic acid substitutions of ribitol teichoic acid + lipoteichoic
  + Addition of L-lysine to phosphatidylglycerol on exposed face of the membrane
• These modifications reduce the negative charge of the cellular envelope to become more electro-neutral, preventing the peptides from binding

Question 4

Enzymatic modification of peptides for antimicrobial peptide resistance

Answer 4

• Staphylokinase is a potent inhibitor of antimicrobial peptides
• Aureolysin cleaves + inactivates antimicrobial peptides

Question 5

S. aureus interactions with the immune system

Answer 5

• Can inhibit neutrophil chemotaxis vis CHIPs inhibitors to prevent itself from being tagged
• Can directly kill leukocytes by toxin production
• Can resist phagocytosis by preveing leukocytes from finding the Fc site on antibodies that are used for phagocytosis recognisation or coat itself with host self-antigens with using its adhesins

Question 6

Differential regulation of virulence factor production

Answer 6

• During exponential phase, it produces surface proteins
• At stationary phase, it produces exoproteins ie toxins

Question 7

Quorum sensing

Answer 7

Quorum sensing is a cell to cell communication form between bacteria by sensing cell population density, adjusting gene expression

Question 8

Quorum sensing in S. aureus

Answer 8

When population density reaches a threshold, it drives transcription of more quorum sensing + RNA3 production

Question 9

RNA3

Answer 9

• Induced when culture reaches a certain population density
• Has multiple regulatory roles:
  + Repression expression of surface proteins
  + Inhibits transcription
  + Pairs with 5’ end of spa mRNA to stop translation of protein A mRNA
  + Induces expression of exoproteins
  + Competes with directly with an intramolecular RNA secondary structure which hides the ribosome binding site. If RNA3 successfully binds to the site, a-haemolysin is expressed

Question 10

Agr

Answer 10

• Agr differentially regulates production of toxins + surface proteins
• Achieved by sensing population density
• Differential regulation required for passage through host cells