MECHANISMS OF ANTIBACTERIAL ACTION AND RESISTANCE

Question 1

1.Inhibitors of cell wall biosynthesis

Answer 1

1.Cycloserine inhibits cell-wall biosynthesis
Inhibits peptide cross link

2.Glycopeptides
Vancomycin, teicoplanin prevents the cell wall from forming cross-links

3.Beta (ß) -lactams
Penicillins
Inhibit the enzyme transpeptidase, which lays down cross links, preventing new cell wall formation.

Question 2

2.Inhibitors of nucleic acid synthesis

Answer 2

1.Inhibitors of synthesis of precursors
sulphonamides- are analogues of PABA. Competes with PABA for active site
trimethoprim- interacts with dihydrofolate reductase

2. Inhibitors of DNA replication
   (fluoro)quinolones
   interact with DNA topoisomerases
   Quinolones stabilise gyrase-DNA complex and lead to dsDNA breaks – causes bacterial cell death
3. Inhibitors of RNA polymerase
   rifampicin
   inhibits RNA polymerase

Question 3

3.Inhibitors of Protein synthesis

Answer 3

Aminoglycosides
(e.g. gentamicin and streptomycin)
bind irreversibly to the 30S subunit of bacterial ribosomes. They may also prevent peptide chain elongation.

Question 4

4.Attacking the cell membrane

Answer 4

Agents that interfere with cell envelope integrity
e.g. polymyxin (e.g. Colistin) integrates in the membrane and creates pores

Question 5

Mechanisms of Resistance

Answer 5

1. Enzymatic resistance
   Bacteria synthesise enzymes that destroy or alter an antibiotic, leading to resistance.
2. Alterations in target site
   Mutations at the target site of the antibiotic reduce the interaction of the antibiotic with its target
3. Metabolic bypass
   Acquisition of new genes that give bacterium an alternative route along a metabolic pathway allowing them to ‘bypass’ the target of the antibiotic.

4) The cell envelope (wall) provides a barrier/s to antibiotics accumulating inside the bacterial cell
active efflux

Question 6

Combination Therapy in Combating Resistance

Answer 6

Combination therapy uses two or more antibiotics to target different bacterial processes simultaneously, reducing the likelihood of resistance development.