Metabolic antagonists: Which compounds act as antimetabolite inhibitors of folate-dependent pathways in bacteria?

Introduction / Context:
Antimetabolites mimic natural substrates, blocking essential biosynthetic steps. In bacteria, folate metabolism is a classic target exploited by sulfonamides and trimethoprim, often combined for synergy.

Given Data / Assumptions:

• Sulfonamides and trimethoprim are being considered for their roles in folate pathway inhibition.
• We are to identify which act as metabolic antagonists.

Concept / Approach:
Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit dihydropteroate synthase, preventing dihydropteroate and subsequently dihydrofolate synthesis. Trimethoprim inhibits dihydrofolate reductase, blocking tetrahydrofolate formation. Together (co-trimoxazole), they produce sequential blockade, enhancing bactericidal effect.

Step-by-Step Solution:
Map pathway: PABA → dihydropteroate → dihydrofolate → tetrahydrofolate. Assign inhibitors: sulfonamides at dihydropteroate synthase; trimethoprim at dihydrofolate reductase. Identify both as antimetabolites (substrate/enzyme analogs). Select the combined option “Both (a) and (b)”.

Verification / Alternative check:
Clinical use of co-trimoxazole (SMX/TMP) in urinary tract infections, Pneumocystis prophylaxis, and nocardiosis reflects their synergistic antimetabolite action.

Why Other Options Are Wrong:
Choosing only one ignores the well-established dual blockade; rifampicin targets RNA polymerase, not folate metabolism.

Common Pitfalls:
Confusing bacteriostatic vs bactericidal effects: individually often bacteriostatic; in combination frequently bactericidal for select organisms.

Final Answer:
Both (a) and (b).