Bypass Mechanisms - A metabolic step which is inhibited by an antimicrobial agent may be replaced (bypassed). Resistance to sulphonamides and to trimethoprim develops when the chromosome coded enzyme is replaced by an entirely new metabolic enzyme that is insensitive to the inhibitor. This permits the blocked pathway to function in the, presence of the drug.
Sulphonamide action: The enzyme dihydropteroate synthetase condenses p aminobenzoic and a reduced pteridine derivative to form dihydropteroate, an intermediate in dihydrofolate biosynthesis. The bacteriostatic effect of sulphonamides is due to competitive inhibition of dihydropteroate synthetase; Trimethoprim acts by inhibiting the dihydrofolate reductases of susceptible bacteria. The two drugs thus block the same biosynthesis pathway to a critical intermediate.





