Mode of action of antibiotics

• What are the 2 essential requirements of antibiotics?

  Must cause disruption to a structure or process that is essential for growth and survival of the microorganism

  Must cause minimal harm to the host organism

  (must be selective)
• Some antibiotics may have narrow therapeutic index which means?

  Although they can kill bacteria, they are also toxic to human cells and may cause unwanted side effects
• Why do some antibiotics need to be carefully monitored?

  To ensure they are therapeutic but not excessively toxic (therapeutic drug monitoring)
• What are the common mechanisms of action of antimicrobials?

  Cell wall synthesis

  DNA replication

  RNA synthesis

  Protein synthesis (50S and 30S)

  Antimetabolites
• What are drugs targeting cell wall synthesis?

  Beta lactam

  Vancomycin
• What are drugs targeting DNA replication?

  Quinolones

  Metronidazole
• What are drugs targeting RNA synthesis?

  Rifampin
• What are drugs targeting protein synthesis 50S?

  Macrolides

  Clindamycin

  Linezolid
• What are drugs targeting protein synthesis 30S?

  Aminoglycosides

  Tetracyclines
• What are drugs targeting antimetabolites?

  Sulfonamides

  Trimethoprim
• What is the differences between bacteriostatic and bacteriocidal antibiotics?

  Bacteriostatic antibiotics prevent bacteria multiplying

  Bactericidal antibiotics kill the bacteria
• What are the modes of attack?

  Breach their wall

  Hack into their information centres

  Disrupt their factories
• What can breach bacteria cell wall?

  Cell wall active agents
• What can hack into bacterial information centres? and what do they do?

  Anti metabolites

  Inhibit RNA synthesis or DNA replication
• How can we disrupt bacterial factories?

  inhibitors of nucleic acid and protein synthesis
• Bacteria need a strong and function cell wall to prevent?

  Cell lysis
• If they cannot synthesise peptidoglycan correctly, what happens?

  Cell wall is compromised
• Agents that disrupt the process of peptidoglycan synthesis are bacteristatic or bacteriocidal?

  Bacteriocidal (kill bacteria)
• What is the difference between gram positive and negative cell wall?

  Positive has a thicker cell wall

  Negative has an outer membrane
• Peptidoglycan synthesis is building of what? catalysed by?

  Building of cross linked chains which is catalysed by specific enzymes (transpeptidases or penicillin binding proteins)
• Beta-lactams bund directly to what preventing cross linking?

  Transpeptidase
• Glycopeptides bind to what preventing cross linking?

  side chains
• What is a beta lactam?

  defines by the presence of a four membered beta lactam ring
• What do beta lactams prevent?

  Cross linking of peptidoglycan structure by inhibiting transpeptidases (PBP) and bacteria die by lysis
• What are the 4 main types of beta-lactam?

  Penicillin, cephalosporin, carbapenem, monobactam
• Many bacteria can produce enzymes that destroy b lactam ring of the antibiotics so what do we use?

  Beta lactamases
• What are beta lactamases?

  large group of enzymes that include ESBL and carbapenemases
• What does b-lactam with b-lactamase inhibitor inhibit?

  Inhibits mop up b-lactamse so antibiotic remains active
• What is coamoxiclav composed of?

  Beta lactamase inhibitior: clavulanate

  B-lactam: Amoxicillin
• What is piptazobactam composed of?

  Beta lactamase inhibitior: tazobactam

  B-lactam: piperacillin
• How does vancomycin work?

  Bind to acyl-D-alanyl-D-alanine of NAM residues and blocks elongation of peptidoglycan backbone
• Vancomycin, a glycopeptide, is only against which bacteria?

  Gram-positive organisms ONLY *eg for tx of MRSA)
• Why can glycopeptides not be used for gram negative?

  Large size means it cannot pass the outer membrane of gram negatives, therefore no gram neg activity
• What is the action of vancomycin?

  Inhibits cell wall crosslinking but in a different way to penicillins
• How does vancomycin inhibit the cell wall?


  Binding of vancomycin to amino acids (d-ala-d-ala) of the tetra-peptides that extend from M sugars, causes steric hindrance that disrupts crosslinking
• Tetrapeptide extend from: ?

  What binds to the tetrapeptides: ?

  M sugars

  vancomycin
• Describe the process behind nucleic acid synthesis inhbitors.

  Bacteria need to replicated their DNA and need to transcribe it to mRNA to specifiy the correct sequence of amino acids to make proteins and enzymes required for survival and growth. Agents that disrupt these processes cause cell death.
• What does DNA gyrase/topoisomerase do?

  Catalyse DNA supercoiling (necessary for DNA replication)
• Negative supercoling is catalysed by? which does what?

  Catalysed by DNA gyrase.

  Relaxes the supercoils by nicking the DNA at specific points so that replication can take place
• What do quinolones inhibit?

  Bacterial DNA gyrase and topoisomerase IV enzymes, thereby inhibiting DNA replication as supercoils cannot be unraveled