Bacterial Targets for Antimicrobial Therapy

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!

Structure of bacteria Differences in structure facilitate selective toxicity

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

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.

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

Protein synthesis

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

Antibiotic resistance

Mechanisms of resistance

Thank-you! Queries, concerns? mzyrh1@nottingham.ac.uk