What is the mechanism of action of beta-lactam antibiotics?

• A. Inhibit cross-linking of peptidoglycan by binding penicillin-binding proteins
• B. Inhibit DNA replication
• C. Inhibit protein synthesis
• D. Disrupt cell membrane integrity

Answer: (A)

Beta-lactam antibiotics work by targeting the bacterial cell wall synthesis. They bind to penicillin-binding proteins, the transpeptidases that cross-link peptidoglycan strands. The beta-lactam ring imitates the normal D-Ala-D-Ala end of the precursor peptidoglycan, so it acylates the active site of PBPs and blocks transpeptidation. Without proper cross-linking, the cell wall weakens, and actively growing bacteria cannot maintain their integrity, ultimately leading to lysis. This action is specific to bacteria because human cells lack a peptidoglycan cell wall.

Inhibiting DNA replication describes agents like fluoroquinolones; inhibiting protein synthesis describes agents such as tetracyclines, macrolides, and aminoglycosides; disrupting cell membrane integrity describes agents like polymyxins or daptomycin.