What is the mechanism of action of isoniazid in the treatment of tuberculosis?

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Multiple Choice

What is the mechanism of action of isoniazid in the treatment of tuberculosis?

Explanation:
The key idea here is that isoniazid works by blocking the construction of the mycobacterial cell wall. It starts as a prodrug that the TB bacterium activates with its own KatG enzyme. Once activated, it inhibits an enzyme (InhA) in the fatty acid synthesis pathway responsible for making mycolic acids, which are essential components of the mycobacterial cell wall. Without proper mycolic acids, the cell wall can’t form correctly, so the bacterium becomes unable to maintain its structure and integrity and dies, especially when it is actively growing. This mechanism is different from drugs that inhibit protein synthesis, stimulate the immune system, or disrupt nucleic acid synthesis, which is why inhibiting cell wall formation is the best description for isoniazid’s action. Note that resistance can arise if the activating katG gene or the target InhA changes, reducing drug activation or binding.

The key idea here is that isoniazid works by blocking the construction of the mycobacterial cell wall. It starts as a prodrug that the TB bacterium activates with its own KatG enzyme. Once activated, it inhibits an enzyme (InhA) in the fatty acid synthesis pathway responsible for making mycolic acids, which are essential components of the mycobacterial cell wall. Without proper mycolic acids, the cell wall can’t form correctly, so the bacterium becomes unable to maintain its structure and integrity and dies, especially when it is actively growing.

This mechanism is different from drugs that inhibit protein synthesis, stimulate the immune system, or disrupt nucleic acid synthesis, which is why inhibiting cell wall formation is the best description for isoniazid’s action. Note that resistance can arise if the activating katG gene or the target InhA changes, reducing drug activation or binding.

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