Trimethoprim, Septra, and Bactrim inhibit folate metabolism. Trimethoprim inhibits the enzyme dihydrofo-late reductase, which is essential for tetrahydrofolate synthesis, whereas sulfonamides inhibit dihydropteroate synthase. Resistance to these antibiotics involves circumventing the effects of the antibiotic by either overpro-tection of dihydrofolate reductase or acquisition of a gene encoding a resistant form of the enzyme. Mutations to dihydrofolate reductase structural gene can also confer resistance.
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