48 and 49 - Antibiotics II

Question 1

What is present in the bacterial “cell wall”?

Answer 1

Peptidoglycan

• Peptidoglycan is present in both Gram-positive & Gram-negative bacterial cells
• The two main things that you need to remember: cell wall is a very rigid structure, composed of disaccharide subunits and a string of amino acids
• The bacteria, when making the wall, will link together the disaccharides and peptides to form the rigid structure
• It is this process that you can disrupt with certain antibiotics

Question 2

What link all the peptides of the stiff bacterial peptidoglycan cell wall together?

Answer 2

Penicillin-binding proteins

Question 3

What is the significance of penicillin-binding proteins?

Answer 3

Peptidoglycan is maintained by the enzymes that create the bonds between NAM-NAG peptidoglycan monomers and between NAM-NAG chains in the layer

Question 4

How can you target the penicillin-binding proteins?

Answer 4

By using penicillin-like antibiotics
- Specific b-lactam antibiotics bind selectively to different PBPs and this contributes to the sensitivity of bacterial strains to individual penicillins and cephalosporin antibacterial agents

Question 5

What are the beta-lactam compounds?

Answer 5

• penicillins
• cephalosporins
• monobactams
• carbapenems

All have the chemical structure of a lactam ring (B).

Question 6

What are many of these drugs susceptible to?

Answer 6

Many are susceptible to the bacterial enzyme b-lactamase which can hydrolyze the lactam ring and render the compound ineffective. b-lactamase is expressed by some bacteria.

Question 7

What does it mean if something is bacteriocidal?

Answer 7

In general, if you inhibit the cell wall, you are bacteriocidal ***

Question 8

What does it mean if something is bacteriostatic?

Answer 8

If we inhibit protein synthesis, you are bacteriostatic ***

Question 9

What are protein synthesis inhibitors?

Answer 9

Include aminoglycosides, macrolides, tetracycline and a few other specific compounds.

Question 10

In general, are protein synthesis inhibitors baceriostatic or bacteriocidal?

Answer 10

In general, these agents exert a bacteriostatic effect but some can be bactericidal.

Question 11

How do protein synthesis inhibitors work?

Answer 11

These agents disrupt the process of translation by targeting the molecular machinery (ribosomal subunits 50S, 30S) needed to translate mRNA to protein.

Question 12

What protein subunits are unique to prokaryotes?

Answer 12

The 70S ribosome (with 50S and 30S subunits)

This means that it is a “selective cytotoxicity”

Question 13

In order to understand the way antibiotics that target translation work, we need to first understand translation (quick review)

Answer 13

Here we go…

Question 14

What is step 1?

Answer 14

Step 1: charged tRNA binds to “A” site

Question 15

What is step 2?

Answer 15

Step 2: peptidyl tRNA, peptide bond formation between growing amino acid chain & new amino acid in “A” site

Question 16

What is step 3?

Answer 16

Step 3: the newly “uncharged” tRNA exits

Question 17

What is step 4?

Answer 17

Step 4: the now-longer amino acid chain translocates to the “P” site