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Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e318279f1ac
Immunology/Microbiology for ID

Common Killing Mechanism for Bactericidal Antibacterial Compounds

Rosenthal, Kenneth S. PhD*; Risley, Kim M. PhD

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Abstract

Abstract: Recent findings identify a common toxic mechanism for drugs within 3 bactericidal antimicrobial families, β-lactams, quinolones, and aminoglycosides, beyond the primary target interaction. In vitro studies show that treatment with these compounds blocks cell division, which promotes a buildup of reduced nicotinamide adenine dinucleotide, and its oxidation promotes the production of reactive oxygen species, including hydroxyl radicals. The hydroxyl radical oxidizes guanine to 8-deoxy-guanine. 8-deoxy-guanine can base pair with both deoxycytosine and deoxyadenosine, and this mismatch promotes mutation. The cell’s effort to repair closely spaced mismatches with 8-deoxy-guanine causes double-strand breaks in the DNA, which kill the bacteria. These findings identify a common killing mechanism for bactericidal drugs and suggest mechanisms that contribute to the intrinsic susceptibility of bacteria to these drugs.

© 2013 Lippincott Williams & Wilkins, Inc.

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