Antibiotics - James Usher Flashcards
What are antibiotics?
Bioavailable compounts that inhibit bacterial growth
- They interfere with specific bacterial enzymes
- And have differential toxicity for bacterial cells
- e.g. target only present in prokaryotic cells, or targets sufficiently different in eukaryotic cells
What class of antibiotics target cell wal synthesis?
- Beta Lactams
- Vancomycin
- Bacitracin
What cross-links peptide side chains for peptidoglycan?
Penicillin-binding protein (transpeptidase) cross links peptide side chains of peptidoglycans
We target this with beta lactam and glycopeptide antibiotics
What is the functional group of penicillin like drugs?
beta lactam ring
Modification of which aspect of beta lactam drugs give them their different properties?
Modification of the R side chains
This affects spectrum, resistance to B-lactamases, bioavailability, pharmacokinetics
How to B-lactams work?
They inhibit the last step in peptidoglycan synthesis by binding irreversibly to penicillin-binding protein by forming a covalent bond with a serine residue in penicillin binding protein.
This inhibits cross-linking of peptide side chains of peptidoglycan backbone, leading to break down of the peptidoglycan layer resulting in cell lysis.
What type of bacteria do glyocpeptides affect, and why is this?
Gram +ve only, since they unable to penetrate gram negative outer membrane due to their size.
e.g. Vancomycin, Teicoplanin
How to glycopeptides affect peptidoglycan synthesis?
Glycopeptides block pentapeptide crosslinking (whilst betalactams block the penicillin binding protein). The glycopeptides recognise the two final amino acids of this, which are both D-alanine-D-alanine (the resistance mechansism to glycopeptides results in a change to this pentapeptide).
Glycopeptides bind to D-alanine-D-alanine portion of muramylpentapeptide, and inhibits corss linking.
How to antibiotics which target protein synthesis kill cells?
They are antibiotics that inhibit protein synthesis by inhibiting ribosomal function.
They bind to 16S or 23S rRNAs in the ribosomal functional sites.
The differences between the prokaryotic and eukaryotic ribosomes allows for differential selectivity.
For antibiotics which target nucleic acid synthesis, how do antibiotics which target folate snythesis work?
They target the bacterial pathway for production of tetrahydrofolic acid (an essential co-factor for synthesis of nucleic acids and fMet)
The two antibiotics in this class are: Sulphonamides, and trimethoprim
How do sulphonamides work?
Competitively inhibits first step (since structurally similar to p-aminobenzoic acid)
How does trimethoprim work?
Competitively inhibits dihydrofolate reductase (is structurally similar to dihydrofolate acid)
How does Metronidazole work?
Makes breaks inthe DNA
It’s a prodrug that reuqires activation by flavodoxin
Spectrum: anaerobes, heliobacter pylori, and certain protozoa
