Antibiotics 2

Question 1

What is the structure of peptidoglycan?

Answer 1

Backbone of N-acetyl glucosamine and N-acetyl muramic acid with a peptide chain coming off the muramic acid and a pentapeptide bridge linking the 3rd residue to the 4th residue of the peptide chain

Question 2

What are the amino acids of the peptide chain in staph aureus?

Answer 2

L-ala, D-glu, L-lys, D-ala

Question 3

What does the alternating pattern of D and L residues give the peptidoglycan?

Answer 3

rigidity

Question 4

How is peptidoglycan synthesised?

Answer 4

The precursors are synthesised in the cytoplasm then transported to the inner aspect of the plasma membrane where synthesis continues - when building block is complete it is transported to the outermembrane where cross linking occurs

Question 5

What is the structure of the building block of the peptidoglycan?

Answer 5

glucosamine and muramic acid bound to a phospholipid, peptide chain with an additional 5th reside of D-ala and the pentaglycine

Question 6

What happens in cross linking of peptidoglycan?

Answer 6

The 5th glycine in the pentapeptide bridge knocks off the terminal D-ala and binds to the subterminal D-ala

Question 7

What enzymes cause cross linking of peptidoglycan?

Answer 7

Transpeptidases (penicllin binding proteins)

Question 8

What is the action of vancomycin?

Answer 8

Binds to terminal D-ala and prevents cross linking of peptidoglycan

Question 9

Which type of bacteria do vancomycin act against?

Answer 9

Gram positive bacteria (can’t get through outer membrane of gram negative bacteria)

Question 10

Why are enterococci resistant to vancomycin?

Answer 10

Because they use a D-lax instead of a terminal D-ala

Question 11

How are vancomycin intermediate resistant staph aureus resistant to vancomycin?

Answer 11

They make extra peptidoglycan to ‘soak up’ vancomycin

Question 12

What is the action of beta lactams?

Answer 12

Blocks the action of the enzyme for cross linking peptidoglycan. This happens because the beta lactam ring is chemical similar to the D-ala D-ala bond - the enzyme binds to beta lactam instead and this binding deactivates the enzyme

Question 13

Is beta lactam bactericidal or bacteriostatic?

Answer 13

Bactericidal because the bacteria recognises that its cell wall isn’t being built properly and produce enzymes to break down their own cell wall and effectively commits suicide

Question 14

What is beta lactamase?

Answer 14

An enzyme in bacteria to act against beta lactam - binds to beta lactam ring and hydrolyses it to make it inactive

Question 15

What are the two kinds of beta lactamases?

Answer 15

Ones encoded on plasmids (e.g. staph aureus) or ones encoded on chromosomes (e.g. pesudomonas)

Question 16

What are altered penicillin-binding proteins?

Answer 16

A bacteria mechanism for avoiding beta lactams - use a PBP that beta-lactam can’t bind to e.g. in MRSA (gene is mecA)

Question 17

Why does antibacterial spectrum of beta lactam antibiotics vary?

Answer 17

• Because different bacteria produce 5-6 different PBP and one particular beta lactam will target only certain PBPs - the more PBPs it binds the bigger its spectrum
  • because the access of the antibiotic to the PBP varies due to different solubility
  • because the susceptibility to beta-lactamase varies

Question 18

What is the action of clavulanic acid?

Answer 18

A beta lactam that inhibits plasmid beta lactamase - on binding beta lactamase it will inhibit the action of beta lactamase and also its own action

Question 19

What is co-amoxyclav?

Answer 19

A combination of clavulanic acid and amoxycillin. Clavulanic acid to inhibit the beta lactamase and amoxycillin to target the PBPs without the threat of beta lactamase.

Question 20

What is the action of ticarcillin?

Answer 20

To treat pseudomonas - inhibits chromosomal beta lactamase

Question 21

Why would you require a combination of ticarcillin and clavulanic acid?

Answer 21

If the pseudomonas had a plasmid with beta lactamase - therefore containing both types of beta lactamase

Question 22

In what ways can antibiotics act on protein synthesis?

Answer 22

recognition, peptidyl transfer, translocation, isoleucyl-tRNA synthesis, formation of initial complex

Question 23

What is the action of aminoglycosides?

Answer 23

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