Inhibitors of Cell Wall Synthesis

Question 1

Name the inhibitors of cell wall synthesis

Answer 1

1) B-Lactams
2) Fosfomycin
3) Cycloserine
4) Bacitracin
5) Vancomycin
6) Dalbavancin
7) Telavancin
8) Oritavancin

Question 2

What is the antibiotic vancomycin classified as?

Answer 2

A glycopeptide

Question 3

Which antibiotics are classified as lipoglycopeptides?

Answer 3

Dalbavancin, Telavancin, and Oritavancin

Question 4

Are all inhibitors of cell wall synthesis bacteriostatic or bactericidal at the clinical dose?

Answer 4

Bactericidal

Question 5

What is the one stipulation when considering whether or not the inhibitors of cell wall synthesis will be useful to treat an infection?

Answer 5

The bacteria have to be replicating

Question 6

What antibiotics have a beta-lactam ring in their structure?

Answer 6

Penicillins, cephalosporins, monobactams, and carbapenems

Question 7

Which antibiotic inhibits the conversion of NAG to NAM?

Answer 7

Fosfomycin

Question 8

Which enzyme is fosfomycin a structural analog of?

Answer 8

Phosphoenolpyruvate

Question 9

What enzyme does fosfomycin inhibit?

Answer 9

enolpyruvate transferase

Question 10

What class of beta-lactamases has better antimicrobial action?

Answer 10

Class 2

Question 11

Which beta-lactamase inhibitors are class 1?

Answer 11

1) Clavulanic acid
2) Avibactam
3) Tazobactam
4) Sulbactam

Question 12

What beta-lactamases are class 1 inhibitors best at inhibiting?

Answer 12

Serine B-lactamases

Question 13

What can happen to carbapenems when attacked by carbapenemases and metallo-B-lactamases?

Answer 13

They can be hydrolyzed which irreversibly inactivates them

Question 14

Which class 1 inhibitor of beta-lactamases is effective against most extended spectrum B-lactamases and carbapenemases?

Answer 14

Avibactam

Question 15

What is the relationship between B-lactams and class 1 B-lactamase inhibitors?

Answer 15

Synergistic

Question 16

What is the relationship between a B-lactam and a carbapenem?

Answer 16

Antagonistic

Question 17

Why is there an antagonistic relationship between a B-lactam and a class 2 B-lactamase inhibitor?

Answer 17

Because carbapenems cause an increase in the release of B-lactamases which destroy the B-lactam antibiotic

Question 18

What are the main mechanisms of resistance to B-lactams in gram-negative bacteria?

Answer 18

Active efflux and impaired drug entry

Question 19

What can a bacterial cell modify in order to prevent B-lactams from being productive?

Answer 19

Penicillin-binding proteins

Question 20

What are the features of a gram-positive bacteria?

Answer 20

They have a thick peptidoglycan cell wall, but they aren’t highly sophisticated

Question 21

What are the features of a gram-negative bacteria?

Answer 21

They have a very thin peptidoglycan layer, but they are highly adaptive

Question 22

What do beta-lactams bind to in order to inhibit cell wall synthesis?

Answer 22

They bind covalently to penicillin-binding proteins

Question 23

What step do beta-lactams inhibit?

Answer 23

Step 5

Question 24

How many domains does the penicillin-binding protein have?

Answer 24

2

Question 25

What are the two domains of the penicillin-binding protein?

Answer 25

The transpeptidase domain and the glycosyltransferase domain

Question 26

Which domain do beta-lactams inhibit?

Answer 26

Only the transpeptidase domain

Question 27

What does the transpeptidase domain do?

Answer 27

It cross-links the polypeptide chains to form the rigid peptidoglycan layer

Question 28

What step does cycloserine inhibit?

Answer 28

2

Question 29

What steps do vancomycin, dalbavancin, telavancin, and oritavancin inhibit?

Answer 29

4 and 5

Question 30

What step does fosfomycin inhibit?

Answer 30

1

Question 31

What step does bacitracin inhibit?

Answer 31

3

Question 32

How do VERSA strands protect themselves against vancomycin?

Answer 32

They add a D-lactate to the end of the D-Ala so that vancomycin can't bind

Question 33

What can vancomycin bind to in order to kill bacterial cells?

Answer 33

They can bind to the terminus of D-Ala-D-Ala and to the pentaglycine bridge

Question 34

What is the result of vancomycin being able to bind to two different binding sites in the bacterial cell?

Answer 34

It can inhibit the transpeptidation step and the transglycosylation step

Question 35

How do VISA strands protect themselves against vancomycin?

Answer 35

They thicken the cell wall by adding more D-Ala-D-Ala residues that are false targets for vancomycin

Question 36

What do dalbavancin, telavancin, and oritavancin share with vancomycin?

Answer 36

a primary mechanism of action

Question 37

What do dalbavancin, telavancin, and oritavancin have that classify them as lipoglycopeptides?

Answer 37

A long, lipophilic side chain

Question 38

What does the lipophilic side chain help telavancin do?

Answer 38

Depolarize the cell membrane and compromise its function

Question 39

What does the lipophilic side chain help oritavancin do?

Answer 39

It dimerizes to strongly anchor itself to the cell membrane improving the ability to bind to targets

Question 40

Studies show that oritavancin can inhibit what?

Answer 40

RNA synthesis

Question 41

Why can oritavancin be used in bacterial infections that are resistant to vancomycin?

Answer 41

Because it has a higher affinity for D-Ala-D-Lactate