Which antibiotic class may interfere with bacterial folate metabolism?

The correct choice is Sulfonamides, as this class of antibiotics directly targets bacterial folate metabolism. Sulfonamides work by mimicking para-aminobenzoic acid (PABA), a substrate involved in the synthesis of folate in bacteria. By competing with PABA for the active site of the enzyme dihydropteroate synthase, sulfonamides inhibit the conversion of PABA to dihydropteroic acid, which is critical for folate production. This disruption ultimately affects bacterial growth and replication since folate is essential for the synthesis of nucleic acids and amino acids.

In contrast, the other classes listed do not directly interfere with folate metabolism. Macrolides inhibit protein synthesis by binding to the 50S ribosomal subunit, while fluoroquinolones target bacterial DNA gyrase and topoisomerase IV to disrupt DNA replication. Aminoglycosides also inhibit protein synthesis but do so by binding to the 30S ribosomal subunit, affecting the translation process. As a result, these antibiotic classes function through different mechanisms and do not have the same impact on folate metabolism as sulfonamides.