Antimicrobials and Antibacterials

Question 1

How do B-Lactams target the biosynthesis of peptidoglycan

Answer 1

• Are affective against growing and diving cells.
• They kill bateria by autolysis (bactericidal)
• Resistant bacterial species produce B-Lactamase- a secreted enzyme which deactivates antibiotics by breaking down their B-Lactam ring.
• They inhibit the enzymes involved in the transpeptidase cross-linking reaction.
• Interfere with linking the indivudual chains together.
• They disrupt peptidoglycan synthesis leading to autolysis
• Penicillins (Penicllin G & Aminopenicillin)
• Very effective against gram negative bacteria but can cause allergic reactions and tolerance can build.
• Cephalosporins
  
  • Cefalexin, Cefazolin (gram positive bacteria)
  • Cefaclor, Cefuroxime (anaerobic bacteria)
  • Cefixime, Cefpodoxime (Gram negative bacteria)
  • Cefepime (pseudomonas)
• Carbapenems
  
  • Meropenem, Ertapenem, Imipenem
  • Broad spectrume, generally effective against all except MRSA and VRE - only available IV.

Question 2

How does Vancomycin target the biosynthesis of peptidoglycan?

Answer 2

• An inhibitor of CW biosynthesis but with a different made of action to B-lactams and a different chemical structure.
• Glycopeptide antibiotic (more allergic reactions)
• Effective against MRSA (IV) but emerging cases of resistance (VRSA, VRE)

Question 3

What are the different groups of antimicrobials/antibacterials

Answer 3

• Antibiotics targeting peptidoglycan biosynthesis- B-Lactams and Vancomycin
• Antibiotics targeting protein synthesis - Tetracycline, Aminoglycosides, Macrolides and Chloramphenicol
• Antibiotics inhibiting DNA biosynthesis - Fluoroquinolones
• Antibiotics inhibiting RNA biosynthesis - Rifampicin
• Drugs targeting Nurcleic Acid biosynthesis - Sulfenamides, Trimethoprim, Co-trimaxazole

Question 4

Explain antibiotics targeting protein synthesis

Answer 4

• Protein synthesis requires rRNA - protein complexes known as ribosomes
• The human ribosomes have 2 subunits (one is 40s (small) and the other is 60s (large))
• Bacterial ribosomes also have 2 subunits but one is 30s (small) and one is 50s (large).
• Some antibiotics bind to and inhibit protein compentents of the 30s subunit:
  
  • Tetracycline
  • Aminoglycosides (Gentamycin, Streptomycin)
• Others bind to and inhibit protein components of the 50s subunit:
  
  • Macrolides (Erythromycin)
  • Chloramphenicol
• All are broad sprectrum (attack positive and negative bacteria)
• Most are bacteriostatic (inhibit/arrest bacteria growth)
• However - associated with greater toxicity

Question 5

Explain how Fluoroquinolones act as antibiotics inhibiting DNA biosynthesis

Answer 5

• Ciprofloxacin
• Norfloxacin
• Levofloxacin
• Moxifloxacin
• Broad spectrum - synthetic.
• Inhibit bacterial enzymes (DNA gyrase) with essential roles in DNA replication
• Effective against gram negative bacteria and intracellular pathogens (legionella, mycoplasma)
• However, they have higher levels of toxicity.

Question 6

Explain antibiotics inhibiting RNA biosynthesis

Answer 6

• RNA biosynthesis requires specialised enzymes known as DNA-dependant RNA polymerase.
• Rifampicin
• Inhibits baterial not human RNA polymerase
• Used predominantly for treating TB

Question 7

Explain drugs targeting Nucleic Acid Biosynthesis

Answer 7

• Biosynthesis of nucleotides requires folic acid.
• Sulfenamides - analogues of PABA (para-aminobenzoic acid) act by substrate competition so that dihydropteroic acid can’t become folic acid.
• Trimethoprim- inhibits dihydrofolate reductase s it can’t become tetrahydrofolic acid which is the last step to the synthesis of nucleotides DNA and RNA
• Co-Trimoxazole- a mixture of both of the above and produces both actions.
• Folic acid synthesis is the target of man-made antibiotics.

Question 8

Bacterial penicillinase (beta-lactamase) inactivates penicillin by cleaving its

Answer 8

β-lactam ring

Question 9

Gram+ve and Gram-ve bacteria differ in

Answer 9

the structure of the cell wall