What is an example of sequential blocking?

• A. Disrupting mitochondrial respiration
• B. Single-agent antibiotic therapy
• C. Combination of penicillin and streptomycin
• D. The use of sulfonamides/PAS and trimethoprim; blocks multiple steps in the folic acid creation pathway for microbes

Answer: (D)

Sequential blocking in antimicrobial therapy means using two drugs that hit two different steps of the same metabolic pathway, producing a stronger overall effect than either alone. In bacteria, folic acid synthesis is a key pathway for making nucleotides needed for DNA replication. Sulfonamides imitate PABA and block dihydropteroate synthase, stopping the pathway at an early step. Trimethoprim then inhibits dihydrofolate reductase, a downstream step. By hitting two successive steps, the pathway is effectively blocked at multiple points, which reduces the ability of the bacteria to compensate and often yields a synergistic effect.

The other options don’t fit this pattern. Disrupting mitochondrial respiration targets energy production as a single process rather than two steps in the same biosynthetic pathway. A single-agent antibiotic therapy involves one drug, not sequential blockade. Two antibiotics that target different processes (cell wall synthesis vs protein synthesis) hit separate functions rather than two consecutive steps in the same pathway, so they illustrate combination therapy rather than sequential blocking.