A laboratory isolate of bacteria shows reduced susceptibility to ciprofloxacin. Sequencing reveals a point mutation in the gyrA gene. Which interpretation best links the genotype to the phenotype?

• A. A mutation in gyrA, which encodes a subunit of DNA gyrase, reduces drug binding to topoisomerase/gyrase and thereby confers decreased ciprofloxacin susceptibility or clinical resistance.
• B. gyrA mutations always increase cell wall thickness preventing ciprofloxacin penetration into the periplasmic space, which explains reduced susceptibility.
• C. A point mutation in gyrA indicates horizontal acquisition of a plasmid-borne beta-lactamase gene which directly degrades ciprofloxacin and causes the observed resistance phenotype.
• D. A mutation in gyrA increases the activity of bacterial RNA polymerase and indirectly neutralizes ciprofloxacin by accelerating transcription so fast that the drug cannot interact with its target.

Answer: (A)