Microbiology MCAT Practice Question
A 34-year-old male with HIV (CD4 count 87 cells/µL) presents with a 6-week history of fever, night sweats, and productive cough. Chest X-ray shows infiltrates in the right upper lobe. Sputum smear microscopy is positive for acid-fast bacilli. He is started on standard first-line tuberculosis therapy with isoniazid (INH), rifampicin, pyrazinamide, and ethambutol. Despite 8 weeks of adherent therapy with documented adequate serum drug levels, repeat sputum cultures remain positive. Susceptibility testing reveals the isolate is resistant to both INH and rifampicin but remains susceptible to pyrazinamide and ethambutol. The isolate possesses intact KatG enzyme and wild-type rpoB gene. Which of the following mechanisms most likely explains this multidrug-resistant phenotype?
Answer choices
- ASpontaneous degradation of isoniazid and rifampicin through increased mycobacterial lipase activity
- BUpregulation of mycobacterial efflux pump genes (such as Rv1258c and Rv2933) encoding transporters that actively extrude both drugs from the cytoplasmCorrect answer
- CMutations in the inhA gene promoter region leading to decreased expression of the enoyl-ACP reductase target enzyme
- DAcquisition of a horizontally transferred plasmid encoding an alternative RNA polymerase resistant to rifampicin inhibition
- EIncreased synthesis of mycobacterial cell wall arabinogalactan that prevents penetration of both INH and rifampicin
- FEnhanced mycobacterial DNA mismatch repair mechanisms that prevent accumulation of lethal drug-induced mutations
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