Pharmacology · Antimicrobials (Cell Wall Inhibitors, Protein Synthesis Inhibitors, Fluoroquinolones)

Fosfomycin is increasingly used for uncomplicated urinary tract infections caused by ESBL-producing E. coli. Its mechanism is:

  • A Covalent binding to penicillin-binding proteins disrupting transpeptidation
  • B Chelation of divalent cations disrupting lipopolysaccharide stability in the outer membrane
  • C Inhibition of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), blocking the first committed step of peptidoglycan synthesis
  • D Inhibition of dihydrofolate reductase blocking folate metabolism
Correct answer: C. Inhibition of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), blocking the first committed step of peptidoglycan synthesis

Explanation

Fosfomycin is a phosphonic acid antibiotic that mimics phosphoenolpyruvate (PEP) and irreversibly inhibits MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), the enzyme catalyzing the first committed step in bacterial peptidoglycan synthesis — the addition of enolpyruvate to UDP-N-acetylglucosamine. Because MurA is structurally distinct from PBPs, fosfomycin retains activity against ESBL-producing Enterobacteriaceae and MRSA. It has unique cellular uptake via glycerol-3-phosphate or glucose-6-phosphate transporters.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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