Lecture 9: Antimicrobials
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What is an antibiotic?
“Chemical produced by a microorganism that kills or inhibits the growth of another organism”
What is an antimicrobial agent?
“Chemical that kills or inhibits the growth of microorganisms”
What are the possible antibacterial results?
• Bactericidal: kills bacteria 2. Bacteriostatic: inhibits growth and reproduction
What are the structural classes of antibiotics
• Beta-Lactam antibiotics • Glycopeptide antibiotics • Tetracyclin antibiotics • Aminoglycoside antibiotics • Macrolide antibiotics
How do antibiotics work? what is their target and mechanism of action?
• Cell Wall synthesis: a. Beta Lactams (penicillins, cephalosporins, carbapenems, monobacams) b. Vancomycin Bacitracin • Nucleic acid/DNA synthesis: a. DNA gyrase - quinolones b. RNA polymerase - rifampin • Protein wall synthesis a. 30s ribosome subunit - tetracyclines, aminoglycosides b. 50s ribosome subunit - macrolides, clindamycin, linezolid, chloramphenicol, streptogramins • Metabolic enzymes a. Folate synthesis - sulfonamides, trimethroprim • Cell membrane - polymyxins
How can bacteria be antibiotic resistant?
• Impermeable cell envelope • Target modification - altering the drugs target • Antibiotic modification - inactivating the antibiotic • Efflux employs genes coding for enzymes that actively pump antibiotic out
what type of antibiotic is penicillin
beta-lactam
How does penicillin function?
• Affects cell wall synthesis • Targets transpeptidases (used in reforming bonds between molecules in peptidoglycan)
How is it penicillin can bind to transpeptidases active site?
Due to its structure resembling D-Ala-D-Ala
What is the resistance mechanism against penicillin
• Antibiotic modification/inactivation 2. Penicillinase (beta-Lactamase)
How does penicillinase work?
• Deactivation of penicillin by hydrolysing the beta-lactam ring • results in penicilloic acid
How do we counteract penicillinase/beta-lactamases?
• “Clavulanic acid” a. Amoxicillin b. Augmentin • binds to beta-lactamases with higher affinity • inhibits action