Question:hard

Pretomanid, a nitroimidazole used in the BPaL/BPaLM regimen for drug-resistant tuberculosis, acts mainly by which mechanism?

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A nitroimidazole prodrug activated by Ddn that blocks cell-wall (mycolic acid) synthesis.
Updated On: Jun 25, 2026
  • Inhibition of mycolic acid synthesis (and generation of reactive nitrogen species), impairing cell-wall formation and anaerobic respiration
  • Inhibition of the RNA polymerase beta-subunit (rpoB)
  • Inhibition of mycobacterial ATP synthase
  • Inhibition of DNA gyrase (topoisomerase II)
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The Correct Option is A

Solution and Explanation

Pretomanid is the "Pa" in the modern short oral regimens BPaL and BPaLM for highly resistant tuberculosis, and identifying its target separates it from its regimen partners.

It is a $\textbf{nitroimidazo-oxazine prodrug}$ that must first be reduced intracellularly by the F420-dependent nitroreductase $\text{Ddn}$. This bioactivation explains its two complementary killing modes. In dividing aerobic bacilli it $\textbf{blocks mycolic acid biosynthesis}$, crippling assembly of the waxy mycobacterial cell wall. In dormant, non-replicating bacilli under anaerobic conditions, the activated drug liberates $\textbf{reactive nitrogen intermediates such as nitric oxide}$ that disrupt respiration and sterilise persistent organisms.

The decoys correspond to its companion drugs and standard agents: rifampicin hits RNA polymerase ($rpoB$), bedaquiline ($B$) blocks mycobacterial ATP synthase, and fluoroquinolones ($L$ = linezolid is a ribosomal agent, while moxifloxacin) target DNA gyrase. None of these is pretomanid’s action.

\[\boxed{\text{Pretomanid: inhibits mycolic acid synthesis + releases reactive nitrogen species}}\]
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