L2 Antibacterial drugs II

Question 1

What antibiotics target cell walls? What antibiotics target the cell membrane?

Answer 1

cell wall/peptidoglycan:
beta-lactams (penicillin)
glycopeptides (vancomycin)
Bacitracin (extracellular)
Fosfomycin (intracellular)

cell membrane:
colistin
daptomycin

Question 2

What antibiotics target protein synthesis?

Answer 2

tetracyclines and aminoglycosides

Question 3

Which type of bacteria has 2 membranes and a thin peptidoglycan layer?

Answer 3

gram-negative

Question 4

Describe gram-positive bacteria

Answer 4

1 membrane and 1 thick peptidoglycan layer

Question 5

Summarize peptidoglycan synthesis

Answer 5

UDP-GlyNAc is transformed into UDP-MurNAc; amino acids are then added with a 2 D-Ala cap at the end); the phosphate group of the UDP binds to the Lipid in the membrane; from here, UDP-GlyNAc can bind to form a two sugar complex; flippase moves these sugars to from the cytoplasm to the periplasm; PBP acts on the sugars to make the peptidoglycan chains (GTase) and crosslink them (TPase); Lipid is recycled for another round

Question 6

What are examples of beta-lactams

Answer 6

penicillins, monobactams, cephalosporina, carbapenems

Question 7

How doe beta-lactams work?

Answer 7

They covalently bind to the TPase domain (via the serine residue) of the PBP thereby inhibiting its normal function in the bacterial cell (which is crosslinking the peptidoglycan chains)

This is because beta-lactams have a beta-lactam ring which is similar in structure to the 2 D-Ala structure

Question 8

TF: beta-lactams are bacteriostatic

Answer 8

F, they are bactericidal

Question 9

Why can beta-lactams be life-threatening?

Answer 9

hypersensitivity which includes anaphylaxis can occur through the IgE antibody reaction

Question 10

What are beta-lactamases

Answer 10

They are enzymes that cleave the beta-lactam rings, rendering beta-lactam antibiotics ineffective. They were developed by bacteria as a resistance mechanism

Question 11

What are beta-lactams often paired with for treatment of bacterial infection?

Answer 11

beta-lactamase inhibitors

Question 12

What is NDM-1?

Answer 12

NDM-1 is a subtype of metallo-beta-lactamase which is highly transmissible and confers resistance to beta-lactams

Question 13

TF: there is a strain of gonorrhea that is resistant to all known antibiotics

Answer 13

True, gonorrhea utilizes all known mechanisms of resistance and is resistant even to the last antibiotic option Ceftriaxone

Question 14

What are glycopeptides

Answer 14

it is a class of antibiotics that inhibits the cell wall (thus most effective on gram-positive bacteria)

vancomycin is a glycopeptide

Question 15

How does vancomycin work?

Answer 15

It binds to the 2 D-Ala portion of the peptidoglycan precursor, thus blocking PBP function in both domains (this is because recognition of the D-Ala terminus is required for proper binding)

Question 16

What antibiotic is used to treat severe C.difficil infections

Answer 16

vancomycin

Question 17

What is a common resistance mutation in response to vancomycin?

Answer 17

Divergent biosynthesis of Lipid II where the 2 D-Ala terminus is changed to a D-Ala-D-Lac terminus (dubbed VanA/VanB/VanD Lipid II)

Thus the strong interactions between vancomycin and the 2 D-Ala are reduced (less affinity)

Question 18

How does Bacitracin work?

Answer 18

It inhibits cell wall synthesis by binding to the undecaprenyl pyrophosphate thus preventing the recycling of the Lipid

Question 19

Which antibiotic(s) is/are nephrotoxic?

Answer 19

Bacitricin and Colistin

*Colistin is also neurotoxic

Question 20

How do lipopeptide antibiotics work? What are examples of lipopeptides?

Answer 20

Colistin and Daptomycin

Colistin works by binding to lipopolysaccharides on the outer membrane (gram-negative bacteria) using its many positively charged amino groups (at neutral pH); this causes the membrane permeability to increase, leading to cell leakage and death
>gram-negative bacteria

Daptomycin works by interacting with the Ca2+ in the cell membrane and forms pores, resulting in cell leakage and death
>gram-positive bacteria

Question 21

Which antibiotic(s) is/are used to treat MRSA and VRE?

MRSA = Methicillin-resistant Staphylococcus aureus

Answer 21

Daptomycin
Tetracyclines

Question 22

Which antibiotic is an intracellular inhibitor from the following: vancomycin, penicillin, fosfomycin, colistin, daptomycin

Answer 22

fosfomycin

Question 23

How does fosfomycin work?

Answer 23

It inhibits the first step of the peptidoglycan synthesis pathway (which is in the cytoplasm) by irreversibly binding to the enzyme required for the the formation of UDP-GlcNAc

Question 24

How do aminoglycosides and tetracyclines work?

Answer 24

They bind to the 30s ribosomal subunit and inhibit protein synthesis. Both diffuse through the porin channels in the outer membrane followed by active transport across the cell membrane

Question 25

What is a postantibiotic effect and give an example

Answer 25

it means the antibiotic still has effects such as suppressing bacterial growth even when under the MIC

Question 26

Why are aminoglycosides reserved for serious infections?

Answer 26

They demonstrate renal, cochlear and vestibular system toxicity

Question 27

What are some mechanisms that can cause aminoglycoside resistance

Answer 27

-decrease influx, increase efflux
-mutations in the 30S ribosomal subunit
-inactivation of the aminoglycosides via modifications of its amino group

Question 28

How are tetracyclines different from aminoglycosides?

Answer 28

They are bacteriostatic and have a broader spectrum