1. Bacterial Targets for Antimicrobial Therapy

2. For an antibiotic to be effective
Reach an inhibitory concentration at the site of infection
Penetrate bacterial cell wall to reach target
Overcome antibiotic resistance mechanisms
Exhibit selective toxicity- kill the bacteria, not the patient!

3. Structure of bacteria
Differences in structure facilitate selective toxicity

4. 1. Inhibits cell wall synthesis
Beta lactams
Glycopeptides (vancomycin)
2. Inhibits protein synthesis
Macrolides
Aminoglycosides (gentamicin)
3. Interferes with DNA synthesis and replication
Sulphonamides
Diaminopyridines
4. Disrupts cell membrane

5. Brick wall synthesis
Mr B is a 65 year old retired builder from Nottingham. He is obsessed with building brick walls, despite pleas from his wife to come home. What actions would you take?
Do nothing
B. Restrain Mr B
Interfere with his cement
Interfere with his bricks
Sit down, talk to Mr B about his problem, try to get to the bottom of it. Should Mr B be referred to a psychiatrist? Support Mrs B and reassure during the process.

6. Cell wall synthesis C55 Lipid carrier NAG NAM NAG Mr B: Bacitracin
Prevent dephosphorylation of phospholipid carrier, prevents regeneration of carrier necessary for synthesis to continue
Interfere with cement: B lactams
e.g. penicillin
Bind to penicillin binding protein, preventing L-lysine-D-ala link
Interefere with bricks: Glycopeptides
e.g. vancomycin
Bind to D-ala-D-ala and prevent insertion of subunit into cell wall

7. Protein synthesis

8. Nucleic acid synthesis and transcription
Transcription (mRNA synthesis)
Nucleic acid synthesis
Folate required

9. Antibiotic resistance

10. Mechanisms of resistance

11. Thank-you!
Queries, concerns?