LECTURE - Staphylococcus Flashcards
Human-associated CoNS (negative staph)
S. epidermidis-like group:
- S. epidermidis
- S. saprophyticus + subsp
- S. haemolyticus
- S. capitis
- S. hominis
- S. pettenkoferi
- S. simulans
- S. warneri
T or F. S. lugdunensis is part of CoPS
F, CoNS
Human-associated CoPS
- S. aureus + subsp
Diseases caused by S. aureus
- Skin infections
- pyogenic
- toxigenic - Systemic infections
- toxigenic
- invasive disease
Skin infections caused by S. aureus: pyogenic
- stye
- boil (furuncle)
- carbuncle (more serious!)
Staphylococcal skin infections: toxigenic
- staphylococcal scalded skin syndrome (SSSS)
- bullous impetigo
Toxin-mediated systemic infections caused by S. aureus
- food poisoning by staphylococcal enterotoxin (SE); causes vomiting + diarrhea
- toxic shock by TSST
- both are superantigens
Superantigens
(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
Systemic infections caused by S. aureus: invasive disease
- pneumonia
- acute endocarditis
- sepsis
- osteomyelitis
S. aureus virulence factors
- adhesins: MSCRAMMs
- toxins: superantigens, etc.
- polysaccharide capsule
- antibiotic resistance
- regulation of surface adhesins (Quorum sensing)
What is the function of MSCRAMMs
- 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)
Four examples of MSCRAMMs
- protein A (binds IgG)
- collagen-binding protein
- fibronectin-binding protein
- clumping factor (binds fibrinogen)
MCRAMMs are proteins identified by unique AA motif:
LPXTG
- attached to the pentaglycine bridge in peptidoglycan by means of the sortase enzyme
protein A vs. regular MSCRAMM
- 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
Toxins that work systemically
- 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
Toxins that work locally in skin infections
- exfoliative toxins
- SSSS and bullous impetigo
- cleaves proteins exclusive to cells of the epidermis (ex: desmoglein-1)
Toxic exoproducts of S. aureus
- 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
S. aureus polysaccharide capsule
- inhibits attachment + antiphagocytic
- conjugated vaccine use? 2/3 MRSA possess one of two capsule serotypes
T or F. The S. aureus polysaccharide capsule is a critical virulence factor
F! Critical virulence determinant for other organisms but not S. aureus (not that significant)
antibiotic resistant S. aureus
- role of mecA and PBP2’
- MRSA (community- vs. hospital-acquired)
- VISA
Organism detects a certain conctn of itself in the body which then triggers a chain in the type of virulence factors it produces
Quorum sensing
S. aureus quorum sensing process
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
endocarditis and other invasive infections
S. lugdunensis )CoNS)
colonization of indwelling catheters, septicemia, endocarditis
S. epidermidis (CoNS)
UTIs
S. saprophyticus (CoNS)
T or F. S.lugdunensis is a constituent of the normal human skin flora
T!
What’s so special about S. lugdunensis?
- 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
T or F. S. epidermidis forms biofilm and contaminates indwelling catheters
T!
Process of biofilm formation
- adhesion and attachment
- monolayer
- accumulation, proliferation, intercellular adhesion processes
- maturation
- may disaggregate from macrocolony => bloodstream (metastatic + embolic complications)
Most common gram + cause of UTI in the hospital
S. saprophyticus
- Propensity to attach makes it the most common gram + cause of urinary tract infection in the hospital
S. saprophyticus virulence factors
- surface protein that can bind fibronectin + erythrocyte membranes (hemaglutinin)
- can assist colonization in different body sites (vagina + bladder)
