Mutation in which of the following genes is responsible for development of INH resistance in mycobacteria?
**Core Concept**
The development of isoniazid (INH) resistance in mycobacteria is a significant concern in the treatment of tuberculosis. It is primarily due to genetic mutations that affect the target of INH, which is the enzyme catalase-peroxidase (KatG) or the target of INH itself, the enzyme inhA.
**Why the Correct Answer is Right**
The correct answer is the gene that encodes the enzyme inhA, which is a key target of INH in mycobacteria. Mutations in the inhA gene can lead to the development of INH resistance by reducing the affinity of INH for the enzyme or by altering the enzyme's activity. This is a major mechanism of INH resistance in mycobacteria. Additionally, mutations in the promoter region of the inhA gene, known as the -15 promoter, can also contribute to INH resistance.
**Why Each Wrong Option is Incorrect**
**Option A:** The katG gene encodes the enzyme catalase-peroxidase, which is responsible for activating INH. Mutations in katG can lead to INH resistance, but this is not the primary mechanism of resistance.
**Option B:** The rpoB gene encodes the beta subunit of RNA polymerase, which is a target of rifampicin, not INH.
**Option C:** The gyrA gene encodes a subunit of DNA gyrase, which is a target of fluoroquinolones, not INH.
**Clinical Pearl / High-Yield Fact**
Mutations in the inhA gene can also lead to cross-resistance to other antitubercular agents, such as ethionamide and thiacetazone.
**Correct Answer:** C. The inhA gene is responsible for development of INH resistance in mycobacteria.