4. Staphylococcus

Main human staph pathogen 

Staphylococcus aureus

Staphylococcal scalded skin syndrome (SSSS)

S. aureus causes redness and blistering of the skin that gives the skin a burned look

S. aureus is the

2nd highest bacterial killer worldwide

Toxins in SSSS

exfoliative toxins A, B, and D

Exfoliative toxins A, B, and D bind to

desmosomes in epidermis called desmoglein-1

Effect of Exfoliative toxins A, B, and D

break down desmoglein-1 and makes the skin cells loose and leads to the separation of skin layers, causing blistering.

Staphylococcal Enterotoxins (SEs)

superantigen that indiuces vomitting

Superantigens

bind to BOTH MHC class II on APC AND TCR on T cell to induce pro-inflammatory cytokines

Why do SEs cause vomitting 

enters through epithelial cells in gut to activate mast cells to produce serotonin which stimulates vagus nerve to induce vomitting 

Toxic shock syndrome toxin-1 (TSST-1)

superantigen that causes severe immune responses and is associated with toxic shock syndrome.

Mobile genetic elements

peices of DNA that can move to other part of genome or in between isolates

Mobile genetic elements in Staph 

Staphyloccocal Pathogenicity Islands (SaPIs)

Staphyloccocal Pathogenicity Islands (SaPIs)

carry the virulence factors including exfoliative toxin D, TSST1, and enterotoxins 

Alpha-toxin

promotes invasion by disrupting the epithelial barrier in 2 mechanisms that both involve host protein ADAM10

1st alpha toxin mechanism

induces pore-formation in host cells

2nd alpha toxin mechanism 

activates ADAM10 to cleave E-cadherin molecules in adherens junctions to
compromises the cytoskeleton

Alpha toxin is normall associated with

pneumonia

Leukotoxin- 4 of them

make pores in host cell membrane that leads to cell lysis.

Leukotoxins are commonly found in 

sepsis cases 

Alpha toxin (alpha hemolysin) is considered

a leukotoxin

S. aureus biofilms

can adhere to indwelling medical devices, tampons, large meat production equipment

S. aureus biofilm adhesion- 1st 

uses adhesins, like MSCRAMMS and other surface proteins, to bind to host tissues and devices.

S. aureus biofilm adhesion- 2

Proliferation where biofilms include proteins, sugars, and DNA

S. aureus biofilm adhesion- 3rd

Dispersion by mechanical forces, like mechanical stress, or by production of proteases and nuclease to break out

Staphylothrombin

cleaves fibrinogen which bind fibrin to surface of cell to shield from innate immune system- molecular mimicry 

Staph surface protein A- SpA

binds to the Fc portion of Igs to decrease opsonisation and phagocytosis

Reactive oxygen species

produced by neutrophils to destroy pathogens (O2-, H2O2, HOCl)

S. aureus protection for ROS 

staphyloxanthin
Superoxide dismutase 
Catalase 

staphyloxanthin

orange pigment that has given S. aureus its name (aureus means golden). This molecule contains a series of double bonds that scavenge radicals originating from ROS activity

Superoxide dismutase

converts superoxide, O2-, to the less toxic H2O2

Catalase 

further detoxify H2O2 by turning it into oxygen gas and water

SCCmec (Staphylococcus cassette chromosome mec)

mobile genetic element that contains the mecA gene, which is responsible for methicillin resistance in S. aureus

MecA

encodes for an alternate penicillin binding protein, PBP2a that is not susceptible to beta-lactam antibiotics

Vancomycin 

last resort of S. aureus

What is the purpose of Staph having so many enzymes for ROS protection

to survive inside neutrophils, which normally kill by producing ROS

Quiz next class

ROS and protections