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1 PID Unit > 7 S. aureus Pathogenesis > Flashcards

7 S. aureus Pathogenesis Flashcards

1
Q

What bacterium is responsible for 90% of all bone infections?

A

Staph aureus

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2
Q

In the case, the infected compound bone fracture was cleaned and re-set. After 6 weeks one bone was not set correctly. Why?

A

edema from the initial breaks

inflammation from infection, leading to more edema

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3
Q

How does osteomyelitis show on a radiograph? (radiopaque/radiolucent)

A

radiolucent where the normal bone opacity would be

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4
Q 
What are the characteristics of staph?
Gram?
shape?
oxygen utilization?
motile?
forms spores?
A

Gram + coccus about 1um in diameter
facultative aerobes/anaerobes
nonmotile
nonspore-former

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5
Q

What are the microbiology lab tests that distinguish staph aureus from other microbes?
How are other staph different?

A

catalase + (distinguish from strep)

coagulase + (other staph coagulase -)

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6
Q

What are the three types of hemolysis?

A

beta - complete lysis of blood agar
alpha - blood agar turning green due to change in oxidation state of iron in blood (from hydrogen peroxide and acids)
gamma - no lysis on blood agar plate

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7
Q

What microbe is responsible for:
500,000 cases of post-surgical infection annually
100,000 cases of infectious endocarditis annually
3K-35K cases of pneumonia (post-influenza)

A

staphylococcus aureus

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8
Q

What is the number 1 cause of blood stream infections?

What is number 2?

A

1) staph epidermidis

2) staph aureus

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9
Q

What diseases is staph aureus responsible for causing?

A 
post-influenza pneumonia
endocarditis
blood stream infections
death in AIDs patients
UTI
skin and soft tissue infections (boils)
bone infections
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10
Q

Staph aureus has a 10 year cycle. What is this significant for?

A

New strains emerge every 10 years (except TSST-1 staph aureus broke the cycle)

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11
Q

Does staph aureus make toxins?

What type of pathogen is it? Intra/extracellular?

A

It makes many cell surface and secreted toxins

It is an extracellular pathogen with regard to PMNs and macrophages

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12
Q

What is staph aureus resistant to?

A

drying and some antibiotics

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13
Q

What are the cell surface virulence factors of staph aureus?

there are 5

A 
bound coagulase protein
fibronectin binding proteins
collagen binding proteins
vitronectin binding proteins
protein A
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14
Q

What is bound coagulase protein? What is its purpose?

A

It is a cell surface virulence factor that converts fibrinogen to fibrin to surround the bacterium with self and to wall itself off

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15
Q

What is protein A? What is its purpose?

A

It is a cell surface virulence factor.

It is a protein with 4 domains that bind the Fc portion of IgG and turn them backwards -> antiphagocytic

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16
Q

What are the secreted virulence factors of staph aureus?

there are 16

A 
free coagulase protein
4 hemolysins: alpha, beta, gamma, delta
hyaluronidase
staphylokinase
lipase
DNases
RNases
proteases
beta-lactamases
PBP2a for methicillin resistance
TSST-1
staphylococcal enterotoxins
staphylococcal exfoliative toxins A & B
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17
Q

What is free coagulase protein? What is its purpose?

A

It is a secreted virulence factor that activates the clotting cascade to presumably wall itself off

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18
Q

What is alpha hemolysin toxin? What is its purpose?

A

It is a secreted virulence factor and is a 30K protein that homo-heptamerizes to form a pore in membranes. It is dermonecrotic for human skin and blocks nerve repolarization. (only hemolytic in rabbits)

19
Q

What is beta hemolysin toxin? What is its purpose?

A

It is a secreted virulence factor, is the hot:cold hemolysin, and is a sphingomyelinase

20
Q

What is gamma hemolysin toxin? What is its purpose?

A

It is a secreted virulence factor, is hemolytic, and is a 2 component hemolysin. There are multiple copies of both parts that come together as hetero-heptamer pore formers.

21
Q

What is delta hemolysin toxin? What is its purpose?

A

It is a secreted virulence factor and a small peptide that either acts as a surfactant to solubilize host cell membranes or is a small pore former

22
Q

Staph aureus can have redundant toxins

T/F

A

yes. this makes determining each toxin’s role in disease difficult

23
Q

What is hyaluronidase? What is its purpose?

A

It is a secreted virulence factor and spreading factor. It is an enzyme that cleaves hyaluronic acid in ground substance

24
Q

What is staphylokinase? What is its purpose?

A

It is a secreted virulence factor and spreading factor. It breaks clots that have formed in walling off the organisms

25
Q

What is lipase? What is its purpose?

A

It is a secreted virulence factor and an enzyme required for growth on the skin. Fatty acids in skin are toxic to bacteria and staphylococci have the ability to survive on the skin because of this

26
Q

What is TSST-1? What receptors does it interact with? What is the result?

A

Toxic shock syndrome toxin-1
Secreted superantigen that cross links MHC-II alpha chain to the variable part of the beta chain of the TCR, resulting in massive cytokines released from macrophages/T cells

27
Q

What diseases is TSST-1 responsible for?

A

menstrual TSS

1/2 of nonmenstrual staphylococcal TSS

28
Q

What are staphylococcal enterotoxins? What types are there? What receptors do they bind?

A

A-E and I and SE-like G, H, J-K

They are superantigens likeTSST-1 except different Vbeta-TCRs stimulated; some have two MHC-II sites

29
Q

What routes of administration of staphylococcal enterotoxins lead to what effects?

A

Oral - vomiting, diarrhea 2-8 hours after ingesting (no fever)
IV or lungs - TSS

30
Q

What are staphylococcal exfoliative toxins? What types are there? What disease is caused in what age? Why are others resistant?

A

A & B
Serine proteases that specifically cleave desmoglein 1 (only found in neonatal epidermis), causing separation of layers of the skin -> scalded skin syndrome in neonates
older individuals are resistant due to the dominance of desmoglein 3 in adult skin

31
Q

T/F

Every staphyloccus aureus strain makes one of the cytolysins and one of the superantigens

A

True

32
Q

Where are most virulence factors found in the bacterial genome?

A

mobile genetic elements: pathogenicity islands, bacteriophages, plasmids

33
Q

T/F

Staph aureus’ core chromosome is relatively nonvirulent.

A

True

34
Q

What are the mechanisms of global regulation of secreted toxin production?

A

Histidine kinases in cell membrane sense oxygen and phosphorylate a response regulator (DNA binding protein). Octapeptides are produced, build up, and will activate Agr C. Then, it activates a response regulator to bind to DNA leading to RNA III production, which leads to delta toxin production and exotoxin transcription.

35
Q

What is the relevance of having an oxygen sensing system as a global regulator?

A

Staph won’t make toxins until oxygen is present. This mechanism makes that happen.
eg. menstrual TSS only happens with oxygen availability

36
Q

How are the MRSA strains classified?

A 
HA-MRSA / CA-MRSA
also by pulse field gel electrophoresis
USA300
USA400
USA200
USA100
37
Q

What DNA coding element is found on HA-MRSA? CA-MRSA?

A

HA-MRSA - SCCmec II

CA-MRSA - SCCmec II or IV

38
Q

What is present in the SCCmec DNA coding element?

A

The gene that encodes PBP2a, which leads to resistance

39
Q

What are the highlights of the USA300 MRSA strain? Diseases it causes?

A

common on skin (lots of alpha toxin production & lipase)
SCCmec IV
causes serious necrotizing pneumonia, usually in children, and soft tissue infections in all ages

40
Q

What are the highlights of the USA400 MRSA strain?

Diseases it causes?

A

SEB+ or SEC+
SCCmecIV
causes serious necrotizing pneumonia and TSS usually in children (nonmenstrual)

41
Q

What are the highlights of the USA200 MRSA strain? Diseases it causes?

A

TSST-1 +
most common on mucosal surfaces
SCCmec II or IV
causes serious necrotizing pneumonia and TSS in all ages; rarely causes skin infections

42
Q

What are the highlights of the USA100 MRSA strain?

A

HA-MRSA

common

43
Q

What are the other Staph aureus virulence factors? These have less importance for virulence.
Has vaccination against any of these been successful?

A
  • capsules: small (more virulent) or large (less virulent)
  • slime (also called polysaccharide intercellular adhesion)
  • Iron-surface proteins (siderophores and related iron uptake systems)

Vaccination has NOT been successful. The only vaccine candidates that have given complete protection are toxoids of exotoxins.

1 PID Unit (12 decks)

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