Discussion
Which of the following is the cause for drug resistance in tuberculosis?
Answer: A
Correct answer: Mutation
Drug resistance in Mycobacterium tuberculosis arises by chromosomal mutation. Resistance to rifampicin comes from mutations in rpoB, to isoniazid from mutations in katG or inhA, and to streptomycin from mutations in rpsL - each altering the drug target or the enzyme that activates the drug.
No plasmids or natural gene-transfer systems of clinical significance are known in M. tuberculosis, so transduction, transformation and conjugation play no part. This is why multidrug resistance in tuberculosis is built up stepwise under inadequate treatment, and why combination therapy - which makes simultaneous mutation to several drugs vanishingly unlikely - is the standard regimen.
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