Beta-lactam antibiotics kill bacteria through penicillin-binding protein (PBP) inhibition. Which process is DIRECTLY impaired when PBPs are inhibited, leading to cell lysis?

• A Synthesis of N-acetylmuramic acid (NAM) precursors in the cytoplasm
• B Transpeptidation — the cross-linking of glycan chains by forming D-Ala-D-Ala peptide bridges in the periplasmic space ✓
• C Translocation of lipid-PP-disaccharide-pentapeptide across the cell membrane via MurJ
• D Transglycosylation — polymerization of NAG-NAM disaccharide units into linear glycan strands

Explanation

PBPs are transpeptidases that catalyze the cross-linking step of peptidoglycan synthesis. They cleave the terminal D-Ala from the pentapeptide chain and form a covalent bond between the D-Ala and the diaminopimelic acid (or lysine) of an adjacent glycan strand. Beta-lactams are structural analogs of the D-Ala-D-Ala substrate and irreversibly acylate the active-site serine of PBPs, blocking transpeptidation. The resulting weakly cross-linked cell wall cannot withstand osmotic pressure, leading to cell lysis. NAM synthesis and transglycosylation occur earlier and are not direct PBP targets; MurJ flippase is the target of compounds like intramycin but not beta-lactams.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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