30. Antibiotics and anti-fungals Flashcards
Briefly compare gram positive, gram negative and mycolic bacteria
- G+ - thick peptidoglycan cell wall
- G- - thin peptidoglycan cell wall between inner membrane and outer lipopolysaccharide membrane
- Mycolic bacteria - like G+, with outer mycolic acid layer
Describe the production of tetrahydrofolate (THF) in prokaryotic nucleic acid synthesis?
Paraaminobenzoate (PABA) => dihydropteroate (DHOp) [DHOp synthase]
=> dihydrofolate (DHF) => tetrahydrofolate (THF) [DHF reductase]
What enzyme releases tension from the prokaryotic DNA to allow DNA replication?
DNA gyrase
Which enzyme produces RNA from prokaryotic DNA template?
RNA polymerase (different from eukaryotic RNA polymerase)
How do Sulphonamides affect bacteria?
- Inhibit DHOp synthase
- Prevent DHOp production
(most bacteria are resistant)
How does Trimethoprim affect bacteria?
- Inhibits DHF reductase
* Prevents THF production
How do Fluoroquinolones affect bacteria?
- Inhibit DNA gyrase + topoisomerase IV
* Prevent unwinding of DNA so it can’t be replicated
How do Rifamycins affect bacteria?
- Inhibit bacterial RNA polymerase
- Reduce subsequent production of proteins required for cell survival
(useful in mycobacterium)
Which antibiotics inhibit bacterial ribosomes (preventing protein production)
- Aminoglycosides
- Chloramphenicol
- Macrolides
- Tetracyclines
Is it generally harder to target G+ or G- bacteria?
G+ as they have a more prominent cell wall
How is the peptidoglycan wall synthesised?
- Pentapeptide created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) and a pentapeptide associates with NAM, forming peptidoglycan
- This is transported from inside the cell to the periplasm (across the cell membrane) by a bactoprenol molecule
- It is incorporated into the cell wall
- Transpeptidase cross-links the pentapeptides
Which antibiotics interfere with the bacterial cell wall and cell membrane?
- Glycopeptides
- Bactitracin
- Beta-lactams
- Lipopeptides
- Polymyxins
How do glycopeptides e.g. vancomycin, inhibit the bacterial cell wall?
Bind the pentapeptide, preventing synthesis
How does bacitracin inhibit the bacterial cell wall?
Inhibits bactoprenol regeneration, preventing transportation
How do beta-lactams inhibit the bacterial cell wall
- Bind covalently to transpeptidase
- This inhibits peptidyglycan incorporation into a cell wall
(carbapenems, cephalosporins, penicillins)
Why are antibiotics targeting cell membranes used more?
Due to antibiotic resistance
What do lipopeptides and polymyxins do to bacteria?
- Lipopeptides - disrupt gram-positive cell membranes
* Polymyxins - bind to LPS and disrupt gram-negative cell membranes
What percentage of bacteria have developed resistance?
Around 70%
What are the causes of antibiotic resistance?
- Unnecessary and inappropriate prescription (50% not required)
- Livestock farming
- Lack of regulation (OTC in Russia etc.)
- Lack of development (few new antibiotics)
What resistance is there to beta-lactams?
- Beta-lactamase
- Hydrolyses the C-N bond of the beta-lactam ring of the antibiotics
• Can also have molecules around the beta-lactam ring, shielding it
- steric hindrance
Is penicillin G (IV) and V (oral) more effective for G+ or G-?
G+
Which penicillins are beta-lactamase resistant?
Flucloxacillin and temocillin
Is Amoxicillin beta-lactamase resistant?
Broad-spectrum, but not resistant
Co-administered with clavulanic acid (confers beta-lactamase resistance)
How can E. coli become resistant to trimethoprim?
- Produces different DHF reductase enzyme, a version not affected by the antibiotic
- Can produce more of the enzyme too for better evasion
