What is known about the genetic basis of resistance in M. tuberculosis?
The phenotypic drug resistance of clinical isolates of M. tuberculosis as determined by conventional methods (e.g, broth and agar proportion.) is explained by the presence of mutations in specific genes. These mutations often consist of only a single nucleotide change in the DNA sequence (i.e., point mutation). For example, >95% of clinical isolates that are resistant to RIF have a single point mutation in an 81-bp region of the rpoB gene know as the RIF resistance determining region (RRDR) (1). Mutations in this region affect binding of RIF to the target; thus, conferring resistance. Similarly, 70-90% of INH resistant isolates can be detected by sequencing the inhA promoter region, the inhA gene, and the katG gene (1). INH resistance can be attributed to mutations in the inhA promoter region which lead to overproduction of the drug target and mutations within katG which inhibit activation of the INH prodrug. Rapid detection of the presence of these mutations in rpoB, inhA, and katG ca
