Common killing mechanism for bactericidal antibacterial compounds

Kenneth S. Rosenthal, Kim M. Risley

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)38-40
Number of pages3
JournalInfectious Diseases in Clinical Practice
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Guanine
Hydroxyl Radical
Pharmaceutical Preparations
Bacteria
Lactams
Double-Stranded DNA Breaks
Poisons
Quinolones
Aminoglycosides
Base Pairing
Cell Division
NAD
Reactive Oxygen Species
Mutation

Keywords

  • 8-deoxy-guanine
  • ampicillin
  • antimicrobials
  • bactericidal
  • DNA damage
  • hydroxyl radical
  • kanamycin
  • killing mechanism
  • norfloxacin

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Common killing mechanism for bactericidal antibacterial compounds. / Rosenthal, Kenneth S.; Risley, Kim M.

In: Infectious Diseases in Clinical Practice, Vol. 21, No. 1, 01.01.2013, p. 38-40.

Research output: Contribution to journalArticle

Rosenthal, Kenneth S. ; Risley, Kim M. / Common killing mechanism for bactericidal antibacterial compounds. In: Infectious Diseases in Clinical Practice. 2013 ; Vol. 21, No. 1. pp. 38-40.
@article{ee6413d9dc5b4051ad88d26e4166dd60,
title = "Common killing mechanism for bactericidal antibacterial compounds",
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.",
keywords = "8-deoxy-guanine, ampicillin, antimicrobials, bactericidal, DNA damage, hydroxyl radical, kanamycin, killing mechanism, norfloxacin",
author = "Rosenthal, {Kenneth S.} and Risley, {Kim M.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1097/IPC.0b013e318279f1ac",
language = "English (US)",
volume = "21",
pages = "38--40",
journal = "Infectious Diseases in Clinical Practice",
issn = "1056-9103",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Common killing mechanism for bactericidal antibacterial compounds

AU - Rosenthal, Kenneth S.

AU - Risley, Kim M.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - 8-deoxy-guanine

KW - ampicillin

KW - antimicrobials

KW - bactericidal

KW - DNA damage

KW - hydroxyl radical

KW - kanamycin

KW - killing mechanism

KW - norfloxacin

UR - http://www.scopus.com/inward/record.url?scp=84872083559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872083559&partnerID=8YFLogxK

U2 - 10.1097/IPC.0b013e318279f1ac

DO - 10.1097/IPC.0b013e318279f1ac

M3 - Article

AN - SCOPUS:84872083559

VL - 21

SP - 38

EP - 40

JO - Infectious Diseases in Clinical Practice

JF - Infectious Diseases in Clinical Practice

SN - 1056-9103

IS - 1

ER -