LECTURE - Staphylococcus

Question 1

Human-associated CoNS (negative staph)

Answer 1

S. epidermidis-like group:

• S. epidermidis
• S. saprophyticus + subsp
• S. haemolyticus
• S. capitis
• S. hominis
• S. pettenkoferi
• S. simulans
• S. warneri

Question 2

T or F. S. lugdunensis is part of CoPS

Answer 2

F, CoNS

Question 3

Human-associated CoPS

Answer 3

• S. aureus + subsp

Question 4

Diseases caused by S. aureus

Answer 4

1. Skin infections
   - pyogenic
   - toxigenic
2. Systemic infections
   - toxigenic
   - invasive disease

Question 5

Skin infections caused by S. aureus: pyogenic

Answer 5

• stye
• boil (furuncle)
• carbuncle (more serious!)

Question 6

Staphylococcal skin infections: toxigenic

Answer 6

• staphylococcal scalded skin syndrome (SSSS)

- bullous impetigo

Question 7

Toxin-mediated systemic infections caused by S. aureus

Answer 7

• food poisoning by staphylococcal enterotoxin (SE); causes vomiting + diarrhea
• toxic shock by TSST
• • both are superantigens

Question 8

Superantigens

Answer 8

(SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically, it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release

Question 9

Systemic infections caused by S. aureus: invasive disease

Answer 9

• pneumonia
• acute endocarditis
• sepsis
• osteomyelitis

Question 10

S. aureus virulence factors

Answer 10

• adhesins: MSCRAMMs
• toxins: superantigens, etc.
• polysaccharide capsule
• antibiotic resistance
• regulation of surface adhesins (Quorum sensing)

Question 11

What is the function of MSCRAMMs

Answer 11

• microbial surface components recognizing adhesive matrix molecules
• coat organism with host antigens: appear self-like to host
• attack to host tissue or plastic implants
• may misdirect antibody response (eg. to fibronectin-binding protein AFTER it has bound to fibronectin)

Question 12

Four examples of MSCRAMMs

Answer 12

• protein A (binds IgG)
• collagen-binding protein
• fibronectin-binding protein
• clumping factor (binds fibrinogen)

Question 13

MCRAMMs are proteins identified by unique AA motif:

Answer 13

LPXTG

- attached to the pentaglycine bridge in peptidoglycan by means of the sortase enzyme

Question 14

protein A vs. regular MSCRAMM

Answer 14

• it’s a special type of MCRAMM
• it doesn’t bind a surface matrix molecule but it DOES have the LPTXG motif in its structure!
• protein A binds IgG through the Fc region rather than the antigen-binding sites in the normal way

Question 15

Toxins that work systemically

Answer 15

• Superantigens: TSST, seven types of SE
  > bind to the outside of the TCR and the MHC II antigen
• activate cytokine secretion in many cells (overproduction) and cause the typical consequences of shock

Question 16

Toxins that work locally in skin infections

Answer 16

• exfoliative toxins
• SSSS and bullous impetigo
• cleaves proteins exclusive to cells of the epidermis (ex: desmoglein-1)

Question 17

Toxic exoproducts of S. aureus

Answer 17

• Staphylokinase or Sak binds to plasminogen to dissolve fibrin in clots but also extracellular matrix fibres, allows spread of infection (esp in combo with hyaluronidase and other proteases)
• pore-forming toxins:
  > alpha-hemolysin: prototype of toxin family; 7 monomers form heptamer in cell membrane (like C9 in MAC)
  > leukocidin: PVL (panton-valentine leukocidin); S & F assemble in multiples (octamer) to form a pore

Question 18

S. aureus polysaccharide capsule

Answer 18

• inhibits attachment + antiphagocytic

- conjugated vaccine use? 2/3 MRSA possess one of two capsule serotypes

Question 19

T or F. The S. aureus polysaccharide capsule is a critical virulence factor

Answer 19

F! Critical virulence determinant for other organisms but not S. aureus (not that significant)

Question 20

antibiotic resistant S. aureus

Answer 20

• role of mecA and PBP2’
• MRSA (community- vs. hospital-acquired)
• VISA

Question 21

Organism detects a certain conctn of itself in the body which then triggers a chain in the type of virulence factors it produces

Answer 21

Quorum sensing

Question 22

S. aureus quorum sensing process

Answer 22

regulation of surface adhesins!!!
- early growth phase = adhesins
- late exponential growth = adhesin genes OFF; exoprotein genes ON as AgrD accumulates w bacterial popln density
- AgrC (sensor) detects AgrD
- AgrC is phosphorylated
- AgrC-P phosphorylates AgrA (ACTIVATOR)
- AgrA-P transcriptionally activates virulence genes = EXPRESSED
=> pus formation

Question 23

endocarditis and other invasive infections

Answer 23

S. lugdunensis )CoNS)

Question 24

colonization of indwelling catheters, septicemia, endocarditis

Answer 24

S. epidermidis (CoNS)

Question 25

UTIs

Answer 25

S. saprophyticus (CoNS)

Question 26

T or F. S.lugdunensis is a constituent of the normal human skin flora

Answer 26

T!

Question 27

What's so special about S. lugdunensis?

Answer 27

- behaves clinically similar to S. aureus - causes fulminant native valve endocarditis - colonize skin and mucous more frequently than S. aureus - more virulent that other CoNS bc of several virulence factors including delta toxin-like hemolytic peptide, variety of adhesins, variety of enzymes (DNase + lipase), lysozyme resistance, biofilm formation, agr regulator

Question 28

T or F. S. epidermidis forms biofilm and contaminates indwelling catheters

Answer 28

T!

Question 29

Process of biofilm formation

Answer 29

- adhesion and attachment - monolayer - accumulation, proliferation, intercellular adhesion processes - maturation - may disaggregate from macrocolony => bloodstream (metastatic + embolic complications)

Question 30

Most common gram + cause of UTI in the hospital

Answer 30

S. saprophyticus | - Propensity to attach makes it the most common gram + cause of urinary tract infection in the hospital

Question 31

S. saprophyticus virulence factors

Answer 31

- surface protein that can bind fibronectin + erythrocyte membranes (hemaglutinin) - can assist colonization in different body sites (vagina + bladder)