Lecture 16 - Antimicrobial Mechanisms and Resistance II Flashcards

1
Q

When are anti-membrane antimicrobials not used as a last resort?

A

In antifungal cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Bonds linking rows of peptidoglycan

A

L-Lysine - Penta-glycine - D-Alanine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Polysaccharides making up peptidoglycan

A

N-acetylmuramic acid

N-acetylglucosamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How are peptidoglycans cross-linked?

A

Penta-glycine displaces 2nd D-Ala on L/D polypeptide.

This is catalysed by transpeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How is peptidoglycan assembled?
1)
2)

A

1) Building blocks are immobilised on the inside of the cell membrane
2) Assembled building blocks are flipped onto cell exterior

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Other names for transpeptidases

A

Endopeptidases

Carboxypeptidases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When was vancomycin first used?

A

In the 1950s, when Staph aureus began to be resistant to beta-lactams.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is MRSA?

A

Methicillin-resistant staph aureus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does methicillin resistance signify?

A

Resistance to almost every other beta lactam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which type of antimicrobial is vancomycin?

A

Glycopeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does vancomycin work?

A

Binds directly to D-ala - D-ala on peptidoglycan precursor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Shape of vancomycin molecule

A

Very large, very charged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why can’t vancomycin be used against G- bacteria?

A

Because it is very large and highly-charged

Can’t pass through thicker cell wall.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which bacteria is vancomycin useful against?

A

Staph aureus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Bacteria innately resistant to vancomycin

A

Gram-, enterococci

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why are enterococci resistant to vancomycin?

A

D-ala - D-ala is replaced by D-ala - D-lac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Danger of VRE

A

Enterococci aren’t pathogenic, but are promiscuous in sharing plasmids, on which vancomycin resistance could be encoded

18
Q

VISA

A

Vancomycin intermediate-resistant staph aureus

19
Q

Mechanism of staph aureus partial vancomycin resistance

A

Produce more peptidoglycan.
As vancomycin inhibits peptidoglycan directly, if there is enough peptidoglycan, there can remain enough to perform function after vancomycin has been used up.

20
Q

Issue with treating VISA

A

Greater amount of peptidoglycan can be overwhelmed with more vancomycin, though vancomycin is toxic in higher doses, so this can be dangerous

21
Q

How do beta-lactams work?

A

1) Bind to transpeptidases
2) Transpeptidases can’t hydrolyse the beta-lactam ring
3) Peptidoglycan can’t be assembled

22
Q

What do transpeptidases hydrolyse?

A

CONH bond between D-ala - D-ala

23
Q

Effect on bacteria of beta-lactams

A

Cell wall is weakened

Bacterial cytoplasm is hypertonic to surrounding tissue fluid, so bacteria swell

24
Q

Action of beta-lactamases

A

Hydrolyse a bond in beta-lactam ring

From O=C-N to O=C-OH NH

25
Q

Resistance to beta lactams
1)
2)

A

1) Beta-lactamase

2) Altered penicillin-binding proteins

26
Q

Why does the bacterial spectrum of beta-lactam antibiotics vary?
1)
2)
3)

A

1) Different bacteria have different penicillin-binding proteins
2) Accessibility of antibiotic to penicillin-binding protein varies
3) Antibiotics have different susceptibilities to beta-lactamases

27
Q

Clavulanic acid
1)
2)
3)

A

1) A beta-lactam antibiotic
2) Binds to beta-lactamases, beta-lactamases can’t hydrolyse clavulanic acid
3) A suicide inhibitor of beta-lactamases

28
Q

Clavulanic acid uses

A

Used to inhibit beta-lactamases

Ineffective if used by itself, but effective if combined with another beta-lactam, EG: amoxycillin

29
Q

How is clavulanic acid administered?

A

1) Equal parts clavulanic acid, amoxycillin.
2) As clavulanic acid and amoxycillin are processed in very similar ways, they are both delivered to the site of infection.

30
Q

Co-Amoxyclav

A

Clavulanic acid and amoxycillin treatment

31
Q

What is Pseudomonas aeruginosa intrinsically resistant to?

A

Beta-lactams

32
Q

Why is Pseudomonas resistant to beta-lactams?

A

Has a beta-lactamase gene in its chromosome

Probably used to help form cell wall

33
Q

Beta-lactams that Pseudomonas is susceptible to

A

Carbenicillin

Ticarcillin

34
Q

Effect of clavulanic acid on Pseudomonas

A

Nothing.

Clavulanic acid can be hydrolysed by Pseudomonas chromosomally-encoded beta-lactamase

35
Q

How can Pseudomonas become resistant to carbenicillin and ticarcillin?

A

If it acquires a beta-lactamase plasmid

36
Q

How can a Pseudomonas with a beta-lactamase plasmid be treated?

A

With ticarcillin and clavulanic acid.

Pseudomonas is susceptible to ticarcillin, but beta-lactamase plasmid degrades it.

Clavulanic acid inhibits plasmid beta-lactamase.

37
Q

Number of beta-lactamases

A

Used to be under 10.

With widespread use of beta-lactams, now over 500

38
Q

Gene encoding altered penicillin-binding proteins

A

MecA

39
Q

What does MecA encode?

A

Altered penicillin-binding protein

Is a transpeptidiase that doesn’t bind beta-lactams

40
Q

Why is ampicillin more orally available than penicillin G?

A

Ampicillin is more lipophilic

41
Q

New Delhi beta-lactamase

A

Destroys most modern beta-lactams

Quickly transferred between bacteria on plasmid

42
Q

New beta-lactamase that can destroy most beta lactams

A

New-Delhi beta-lactamase