Killing by Bactericidal Antibiotics Does Not Depend on Reactive Oxygen Species

  title={Killing by Bactericidal Antibiotics Does Not Depend on Reactive Oxygen Species},
  author={Iris Keren and Yanxia Wu and Julio Inocencio and Lawrence R. Mulcahy and Kim Lewis},
  pages={1213 - 1216}
Antibiotic Mechanisms Revisited Several recent studies have suggested that bactericidal antibiotics kill cells by a common mechanism involving reactive oxygen species (ROS). Two groups tested this hypothesis using diverse experiments, with both finding that quinolone, lactam, and aminoglycoside antibiotics had similar efficacy for killing in the presence or absence of oxygen (or nitrate). Liu et al. (p. 1210) saw no increase in hydrogen peroxide production in antibiotic-exposed cells and found… 

Influence of Reactive Oxygen Species on De Novo Acquisition of Resistance to Bactericidal Antibiotics

Results indicate that de novo acquisition of resistance to the bactericidal drugs tested involves a common cellular response that provides protection against ROS accumulation upon exposure to this type of antibiotics.

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

Clinical relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells and these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids.

Reactive Oxygen Species Play an Important Role in the Bactericidal Activity of Quinolone Antibiotics.

It was shown that selective perturbation of the 8oxodGTP incorporation activity of PolIV results in considerable enhancement of the survival of bacteria in the presence of the norfloxacin antibiotic, indicating that ROS induced in bacteria by the presenceof antibiotics in the environment contribute significantly to cell lethality.

Oxygen Limitation Suppresses Reactive Oxygen Species Formation by Norfloxacin

The data suggests that oxygen was required for norfloxacin induced increase in the formation of oxygen radicals, in a mechanism which is likely independent of cytochrome bo activity.

Kalghatgi Damage in Mammalian Cells Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative

It is suggested that not only does oxidative damage to mammalian tissues occur with long-term use of antibiotics, but it is also suggested that this damage could be reversed by the Mice treated with clinically relevant doses of bactericidal antibiotics similarly showed signs of oxidative damage transport chain, which would lead to a buildup of ROS.

Moving forward with reactive oxygen species involvement in antimicrobial lethality.

Distinctions among primary lesion formation, resistance, direct lesion-mediated killing and a self-destructive stress response are discussed to facilitate efforts to potentiate ROS-mediated bacterial killing and improve antimicrobial efficacy.

Imidazoles Induce Reactive Oxygen Species in Mycobacterium tuberculosis Which Is Not Associated with Cell Death

It is demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis, and the untreated mutant strain had a metabolic profile similar to the wild-type drug-treated cells, suggesting that adaptation to similar stresses may play a role in econazole resistance.

Bacterial death from treatment with fluoroquinolones and other lethal stressors

Action of non-quinolone antibacterials and non-antimicrobial stressors is described to provide a general framework for understanding stress-mediated, bacterial death.

Antimicrobial-Mediated Bacterial Suicide

Experimental observations fit well with the concept that bacteria respond to severe stress by building up ROS levels and self-destructing, and a potential consequence of ROS-mediated antimicrobial action is reduced antimicrobial effectiveness when antioxidants are consumed as nutritional supplements during antimicrobial therapy.



Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

It is shown that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals, and that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections.

Oxidation of the Guanine Nucleotide Pool Underlies Cell Death by Bactericidal Antibiotics

The efforts to understand why DinB (DNA polymerase IV) overproduction is cytotoxic to Escherichia coli led to the unexpected insight that oxidation of guanine to 8-oxo-guanine in the nucleotide pool underlies much of the cell death caused by both DinB overproduction and bactericidal antibiotics.

Contribution of Oxidative Damage to Antimicrobial Lethality

Hydroxyl radicals then enhance antimicrobial lethality, as suggested by earlier work, and findings indicate that oxidative stress networks may provide targets for antimicrobial potentiation.

Mechanisms of action of antimicrobials: focus on fluoroquinolones.

  • D. Hooper
  • Biology, Chemistry
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2001
Studies of fluoroquinolone-resistant mutants and purified topoisomerases indicate that many quinolones have differing activities against the two targets, and drugs with similar activities against both targets may prove less likely to select de novo resistance.

Phenotypic Tolerance: Antibiotic Enrichment of Noninherited Resistance in Bacterial Populations

It is demonstrated that tolerant subpopulations generated by exposure to one concentration of an antibiotic are also tolerant to higher concentrations of the same antibiotic and can be tolerant to antibiotics of the other four types.

Inhibitors of Reactive Oxygen Species Accumulation Delay and/or Reduce the Lethality of Several Antistaphylococcal Agents

ABSTRACT Perturbation of hydroxyl radical accumulation by subinhibitory concentrations of 2,2′-bipyridyl plus thiourea protects Escherichia coli from being killed by 3 lethal antimicrobial classes.

Rapid Killing of Acinetobacter baumannii by Polymyxins Is Mediated by a Hydroxyl Radical Death Pathway

This study is the first to demonstrate that polymyxins induce rapid killing of A. baumannii and other Gram-negatives through hydroxyl radical production, which significantly augments the understanding of the mechanism ofpolymyxin action, which is critical knowledge toward the development of adjunctive therapies.