How do beta-lactam antibiotics kill bacteria?

• A. They inhibit penicillin-binding proteins (transpeptidases), preventing cross-linking of peptidoglycan and weakening the cell wall.
• B. They inhibit DNA gyrase and topoisomerase IV.
• C. They block the 30S ribosomal subunit.
• D. They disrupt outer membrane integrity.

Answer: (A)

Beta-lactam antibiotics kill bacteria by inhibiting the enzymes that cross-link peptidoglycan in the cell wall. They bind to penicillin-binding proteins, the transpeptidases that form the cross-links between peptidoglycan strands. The beta-lactam ring mimics the normal substrate and irreversibly inactivates these enzymes, preventing cross-link formation. Without strong cross-links, the cell wall becomes weak, and actively growing bacteria cannot maintain integrity, leading to osmotic lysis and death. Humans don’t have cell walls, so these drugs selectively target bacteria. Other mechanisms listed belong to different antibiotic classes: DNA gyrase/topoisomerase inhibitors block DNA replication, 30S ribosomal blockers disrupt protein synthesis, and outer membrane disruptors compromise the bacterial envelope rather than cell-wall synthesis.