CommonMechanism of Killing by Bactericidal

Antibiotics

The primary drug-target interactions (aminoglycoside

with the ribosome, quinolone with

DNA gyrase, and b-lactam with penicillin-binding

proteins) stimulate oxidation of NADH via

the electron transport chain that is dependent

upon the TCA cycle. Hyperactivation of the

electron transport chain stimulates superoxide

formation. Superoxide damages iron-sulfur

clusters, making ferrous iron available for oxidation

by the Fenton reaction. The Fenton reaction

leads to hydroxyl radical formation,

and the hydroxyl radicals damage DNA, proteins,

and lipids, which results in cell death.

Cell 130,