Beta-lactam antibiotics exert their effect by inhibiting which bacterial proteins?

• A. They inhibit 70S ribosomes
• B. They disrupt bacterial membranes
• C. They inhibit penicillin-binding proteins to block cross-linking
• D. They intercalate into DNA

Answer: (C)

Beta-lactam antibiotics work by targeting the enzymes that cross-link the bacterial cell wall, the penicillin-binding proteins. They resemble the normal substrate used in peptidoglycan synthesis and bind to the active site of PBPs, forming a stable acyl-enzyme complex that blocks the transpeptidation step. Without cross-linking, the peptidoglycan network is weakened, especially as the bacteria grow, leading to cell lysis.

The other mechanisms described aren’t how beta-lactams act: antibiotics that inhibit ribosomes stop protein synthesis; those that disrupt membranes directly damage the cell envelope; and compounds that intercalate into DNA affect genetic material. Resistance can occur through beta-lactamases that hydrolyze the drug or through altered PBPs that bind the antibiotic less effectively, which is why some beta-lactams are paired with beta-lactamase inhibitors or are designed to bind altered PBPs.