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Microbiology · Bacteriology: katG isoniazid resistance
Sample itemA Mycobacterium tuberculosis isolate shows high-level isoniazid resistance. Sequencing finds a mutation in the katG gene. How does this mutation cause resistance?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. Loss of the catalase-peroxidase that activates the prodrug
Isoniazid is a prodrug activated by the mycobacterial catalase-peroxidase encoded by katG. Mutations such as S315T reduce activation and give high-level resistance, whereas inhA promoter mutations cause lower-level resistance.
Option by option
A. Loss of the catalase-peroxidase that activates the prodrug (correct)
Correct. Without the activating enzyme, isoniazid never becomes active.
B. Loss of pyrazinamidase activity
Loss of pyrazinamidase (pncA mutation) causes pyrazinamide resistance.
C. Altered arabinosyl transferase enzyme
Altered arabinosyl transferase (embB) causes ethambutol resistance.
D. A mutated RNA polymerase beta subunit
A mutated RNA polymerase beta subunit (rpoB) causes rifampicin resistance.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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