Lecture 32 - Staph Aureus Flashcards

1
Q

Features of Staph aureus
1)
2)
3)

A

1) Gram + cocci
2) Non-motile
3) Facultative anaerobes

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2
Q
Where does Staph aureus normally inhabit?
1) 
2) 
3) 
4)
A

1) URT
2) Skin
3) Vagina
4) Intestine

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3
Q
Examples of SA virulence factors
1) 
2) 
3) 
4)
5)
6)
7)
A

1) Exfoliative toxins
2) Enterotoxins
3) Haemolysins
4) Lipases, proteases, DNAases
5) Leukocidins
6) Protein A
7) Beta-lactamase

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4
Q

Protein A

A

Binds Fc of IgG

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5
Q

Most common serious SA infections
1)
2)
3)

A

1) Haematogenous spread
2) Endocarditis
3) Osteomyelitis

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6
Q

How long did it take SA to become resistant to penicillin?

A

1-2 years

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7
Q

How long did it take SA to become resistant to methicillin?

A

Under 1 year

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8
Q

How long did it take for 25% of SA in hospitals to be resistant to penicillin?

A

6 years

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9
Q

How long did it take for 25% of SA in hospitals to be resistant to methicillin?

A

20 years

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10
Q

Is MRSA more or less virulent than normal SA?

A

Less virulent

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11
Q

Number of people in the USA who are colonised with SA

A

89.4 million

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12
Q

When is SA most dangerous?

A

When it gets into the bloodstream, causes metastatic infections (endocarditis, osteomyelitis/septic arthritis, discitis/epidural abscesses)

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13
Q

SA bacteraemia incidence in Australia

A

35/100,000 people

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14
Q

ANZCOSS
1)
2)
3)

A

1) Australia New Zealand Cooperative on Outcomes in Staphylococcal sepsis
2) Prospective observational cohort study of Staph bloodstream infections
3) Shows that chance of dying of staph bacteraemia increases with age

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15
Q

Size of SA genome

A

2.8MB

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16
Q

Proportion of SA genome that is core genome

A

~75%

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17
Q

Amino acid conservation of core genome between SA strains

A

98-100%

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18
Q
Contents of SA core genome
1) 
2) 
3) 
4)
5)
6)
7)
A

1) Central metabolism
2) Hose keeping
3) Protein A
4) Capsule
5) Coagulase
6) Protease
7) Fibrinogen-binding proteins

19
Q
How can the accessory genome be constructed?
1) 
2) 
3) 
4)
A

1) Phage
2) Genomic islands
3) Pathogenicity islands
4) Plasmids and transposons

20
Q

Contents of pathogenicity islands in SA
1)
2)

A

Superantigens, such as

1) tst
2) Enterotoxins

21
Q

Contents of transposons and plasmids in SA accessory genome

A

Antibiotic resistance genes

22
Q

Staphylococcal cassette chromosome

A

Contains mecA

23
Q

What is the Staphylococcal cassette chromosome found in?

A

MRSA

24
Q

In the Artemis tool, what show up as blue?

A

Parts of the accessory genome

25
Q

Is high-level vancomycin resistance common in SA?

A

No. Quite rare

26
Q

What confers high-level vancomycin resistance?

A

VanA from VRE

27
Q

What does the VanA gene do?
1)
2)

A

1) Confers high-level vancomycin resistance

2) Encodes a ligase that replaces d-ala-d-ala with d-ala-d-lac

28
Q

High-level vancomycin resistance MIC

A

Over 16mg/L

29
Q

Where does vancomycin act in bacteria?

A

High rate of diffusion through the division septa of bacteria.
Where new cell wall is made

30
Q

Vancomycin intermediate Staph aureus (VISA) vancomycin MIC

A

4-8mg/L

31
Q

A way to measure vancomycin resistance in SA

A

Population analysis

32
Q

What is population analysis?

A

Culture SA in different concentrations of vancomycin, see how many colonies grow. Can be used to calculate MIC

33
Q

What is the VISA phenotype associated with?

A

Cell wall thickening

34
Q

Last-resort antibiotic for MRSA treatment

A

Linezolid

35
Q

What are GraS, VraS?
1)
2)
3)

A

1) Membrane-bound sensors in SA
2) 2-component regulators
3) Might be activated in response to vancomycin, contribute to VISA phenotype

36
Q

SA 2 component regulators

A

1) GraS

2) VraS

37
Q

How do GraS and VraS work?
1)
2)

A

1) Sensor regions detect a stimulus

2) VraR, GraR bind to DNA, change transcription

38
Q
Effects of stimulating VraS and GraS
1)
2)
3)
4)
5)
A

1) Alanation of membrane teichoic acids increases +ve charge of membrane, reducing vancomycin diffusion
2) Thickening of cell wall
3) Decrease in exotoxin production
4) Reduced protein A
5) Increased capsule

39
Q

Is VISA very common?

A

Not at the moment.

It is likely to become more common

40
Q

How does VISA evolve?

A

Appears to accumulate mutations in regulatory genes

41
Q

walR gene
1)
2)
3)

A

1) A 2 component regulator
2) Controls cell wall synthesis
3) Present in division septum cell wall

42
Q
Effect of mutant walR 
1)
2)
3)
4)
A

1) Might be responsible for VISA phenotype
2) Mutation of A to G changes lysine to arginine
3) Reduced autolysin production
4) Increased cell wall production

43
Q

Autolysin role

A

Involved in cell wall turnover in SA

44
Q

How do we know that mutant walR is responsible for VISA?

A

Koch’s molecular postulates (gene removed, lost VISA. Gene placed in vanc-sensitive SA, became VISA)