Fluoroquinolone resistance in E. coli most commonly arises through which primary mechanism that enables subsequent higher-level resistance development?

• A Chromosomal mutation in gyrA (Ser83→Leu and Asp87→Asn) reducing quinolone affinity for the DNA-gyrase complex as the primary high-level resistance mechanism ✓
• B Plasmid-mediated QnrB proteins that mimic DNA and protect topoisomerases from quinolone binding
• C Activation of AcrAB-TolC efflux pump as the sole mechanism sufficient for clinical fluoroquinolone resistance
• D Enzymatic acetylation of the C-7 piperazine moiety by AAC(6')-Ib-cr enzyme as the primary mechanism

Explanation

Primary clinical fluoroquinolone resistance in E. coli is driven by chromosomal mutations in gyrA (the dominant target for ciprofloxacin) — particularly the double mutation Ser83Leu + Asp87Asn — which reduces the quinolone:DNA-gyrase binding affinity substantially. Subsequent mutations in parC (topoisomerase IV), efflux pump upregulation (AcrAB-TolC), and plasmid-mediated Qnr proteins act as stepwise additions. QnrB provides low-level protection and selects for chromosomal mutations. AAC(6')-Ib-cr modifies certain quinolones but cannot confer high-level resistance alone.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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