Describe how a point mutation in the rpoB gene of Mycobacterium tuberculosis can lead to resistance against the antibiotic rifampicin. Mention a specific mutation and its effect on the drug target.
Answer
A C→T transition at codon 531 (Ser→Leu) in rpoB alters the β‑subunit of RNA polymerase, reducing rifampicin binding and conferring resistance.
Step-by-step solution
- State that rpoB encodes the β‑subunit of RNA polymerase, the target of rifampicin.
- Explain that rifampicin binds to a pocket in the β‑subunit to block transcription initiation.
- Describe a point mutation, e.g., C→T at nucleotide position leading to Ser531Leu substitution.
- Show that this amino‑acid change modifies the binding pocket, lowering rifampicin affinity.
- Conclude that the bacterium can continue transcription despite the drug, resulting in resistance.
Common mistake: Confusing rpoB mutation with mutations in other genes like gyrA
Concept tested: Mutation‑driven antibiotic resistance
Published · How this solution was prepared and checked
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