48 and 49 - Antibiotics II Flashcards
What is present in the bacterial “cell wall”?
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
What link all the peptides of the stiff bacterial peptidoglycan cell wall together?
Penicillin-binding proteins
What is the significance of penicillin-binding proteins?
Peptidoglycan is maintained by the enzymes that create the bonds between NAM-NAG peptidoglycan monomers and between NAM-NAG chains in the layer
How can you target the penicillin-binding proteins?
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
What are the beta-lactam compounds?
- penicillins
- cephalosporins
- monobactams
- carbapenems
All have the chemical structure of a lactam ring (B).
What are many of these drugs susceptible to?
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.
What does it mean if something is bacteriocidal?
In general, if you inhibit the cell wall, you are bacteriocidal ***
What does it mean if something is bacteriostatic?
If we inhibit protein synthesis, you are bacteriostatic ***
What are protein synthesis inhibitors?
Include aminoglycosides, macrolides, tetracycline and a few other specific compounds.
In general, are protein synthesis inhibitors baceriostatic or bacteriocidal?
In general, these agents exert a bacteriostatic effect but some can be bactericidal.
How do protein synthesis inhibitors work?
These agents disrupt the process of translation by targeting the molecular machinery (ribosomal subunits 50S, 30S) needed to translate mRNA to protein.
What protein subunits are unique to prokaryotes?
The 70S ribosome (with 50S and 30S subunits)
This means that it is a “selective cytotoxicity”
In order to understand the way antibiotics that target translation work, we need to first understand translation (quick review)
Here we go…
What is step 1?
Step 1: charged tRNA binds to “A” site
What is step 2?
Step 2: peptidyl tRNA, peptide bond formation between growing amino acid chain & new amino acid in “A” site
