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Index >> Bacterial Cheomotherapy >>Bypass Mechanisms

Bypass Mechanisms

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.

In many cases sulphonamide resistance is due to the inhibition of its transport by the R plasmid product. In E. coli, Citrobacter sp. and Klebsiella pneumoniac, however, there is evidence that the resistance is due to a plasmid determined enzyme, dihydropteroate synthetase (MW 45,000-50,000). This enzyme is not affected by sulphonamides. Several examples of plasmid mediated sulphonamide resistance arc known, and it is possible that the mechanism may not be indentioal in all the cases.

The sulphonamide transposable elements (Tnβ). are associated with sulphonamide resistance. They also carry resistance to ampicillin and streptomycin in one case, and to streptomycin and chloramphenicol in the other. Synergistic drug combinations of sulphonamides and trimethoprim ace currently being used. Bacteria resistant to this combination have been isolated.

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