**Core Concept**
Tuberculosis (TB) resistance development is a complex process involving genetic mutations, epigenetic modifications, and environmental factors. The primary mechanism of resistance involves the selection of pre-existing non-susceptible mutants within the TB population.

**Why the Correct Answer is Right**
The correct answer is related to the genetic mutations in the TB bacteria. Specifically, resistance to isoniazid, a first-line antitubercular drug, is often due to mutations in the katG gene, which encodes the enzyme catalase-peroxidase. This enzyme is essential for the activation of isoniazid to its active form. Mutations in the katG gene can lead to a non-functional enzyme, resulting in resistance to isoniazid.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect as it does not accurately describe the primary mechanism of resistance development in TB.

**Option B:** This option is incorrect as it is unrelated to the genetic mutations involved in TB resistance.

**Option C:** This option is incorrect as it describes a different mechanism of resistance development, not relevant to TB.

**Clinical Pearl / High-Yield Fact**
Resistance to antitubercular drugs can develop rapidly, especially in the absence of appropriate treatment. It is essential to follow strict treatment regimens and monitor for resistance development to prevent the spread of drug-resistant TB.

**Correct Answer: D. Genetic mutations in the katG gene leading to a non-functional catalase-peroxidase enzyme.**