A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 61-year-old woman who recently emigrated from India comes to the physician because of a 2-month history of fever, fatigue, night sweats, and a productive cough. She has had a 5-kg (11-lb) weight loss during this period. She has a history of type 2 diabetes mellitus and poorly controlled asthma. She has had multiple asthma exacerbations in the past year that were treated with glucocorticoids. An x-ray of the chest shows a cavitary lesion of the posterior apical segment of the left upper lobe with consolidation of the surrounding parenchyma. The pathogen identified on sputum culture is found to be resistant to multiple drugs, including streptomycin. Which of the following mechanisms is most likely involved in bacterial resistance to this drug?
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A
Alteration in the sequence of gyrA genesIncorrect. Alteration in gyrA confers resistance to fluoroquinolones (which target DNA gyrase), not streptomycin.
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B
Inhibition of bacterial synthesis of RNAIncorrect. Inhibition of RNA synthesis is the mechanism of rifampin; rifampin resistance occurs via rpoB mutations, not the mechanism in question.
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C
Alteration in 30S ribosomal subunitCorrect. streptomycin and other aminoglycosides bind the 30S ribosomal subunit; resistance arises from mutations in 30S components (rpsL, 16S rRNA).
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D
Upregulation of mycolic acid synthesisIncorrect. Mycolic acid synthesis is targeted by isoniazid; upregulation isn't a major resistance mechanism for streptomycin.
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E
Beta-lactamase-mediated drug hydrolysisIncorrect. Beta-lactamase enzymatic hydrolysis confers resistance to beta-lactam antibiotics (penicillins, cephalosporins), not aminoglycosides like streptomycin.
↑ Tap an answer to reveal the reasoning
Answer: C. Streptomycin is an aminoglycoside, and aminoglycosides bind irreversibly to the 30S ribosomal subunit, causing misreading of mRNA and inhibition of protein synthesis. Bacterial resistance to streptomycin in Mycobacterium tuberculosis classically occurs through mutations that alter the 30S ribosomal subunit — specifically in the rpsL gene (encoding the S12 ribosomal protein) or the rrs gene (encoding 16S rRNA). These mutations prevent streptomycin from binding to its ribosomal target.
This patient has reactivation tuberculosis — recent emigration from India (high-prevalence region), chronic glucocorticoid use for asthma (immunosuppression), and the classic cavitary upper-lobe lesion with constitutional symptoms. Multidrug-resistant TB (MDR-TB) is defined by resistance to at least isoniazid and rifampin, often with concurrent streptomycin resistance.
Quick mechanism review for the distractors: gyrA mutations confer fluoroquinolone resistance; rifampin inhibits RNA synthesis (binding the beta subunit of RNA polymerase) and resistance is via rpoB mutations; mycolic acid synthesis is the target of isoniazid (via KatG/InhA), not streptomycin.
**Why each option:**
**A.** Alteration in gyrA confers resistance to fluoroquinolones (which target DNA gyrase), not streptomycin.
**B.** Inhibition of RNA synthesis is the mechanism of rifampin; rifampin resistance occurs via rpoB mutations, not the mechanism in question.
**C.** Correct — streptomycin and other aminoglycosides bind the 30S ribosomal subunit; resistance arises from mutations in 30S components (rpsL, 16S rRNA).
**D.** Mycolic acid synthesis is targeted by isoniazid; upregulation isn't a major resistance mechanism for streptomycin.