Bacteria cannot absorb Folic Acid from medium, which is required for growth and reproduction. In contrast, human cells obtain Folic Acid from diet as Vitamin.
So bacteria have to synthesize Folic Acid inside the cell using Para-amino benzoic acid with the help of certain enzymes.
Sulphonamides being structural analogs of PABA (Para Amino Benzoic Acid) inhibit the pathway of Folic Acid synthesis and growth of bacteria becomes arrested.
Sulfonamides inhibit the “Dihydropteroate Synthetase”, while Trimethoprim inhibits the “Dihydrofolate Reductase (DHFR)”. So a combination of these two drugs block the two successive steps of DNA synthesis and results into bactericidal action.
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