Unraveling the physiological complexities of antibiotic lethality.

@article{Dwyer2015UnravelingTP,
  title={Unraveling the physiological complexities of antibiotic lethality.},
  author={Daniel J. Dwyer and James J. Collins and Graham C. Walker},
  journal={Annual review of pharmacology and toxicology},
  year={2015},
  volume={55},
  pages={
          313-32
        }
}
We face an impending crisis in our ability to treat infectious disease brought about by the emergence of antibiotic-resistant pathogens and a decline in the development of new antibiotics. Urgent action is needed. This review focuses on a less well-understood aspect of antibiotic action: the complex metabolic events that occur subsequent to the interaction of antibiotics with their molecular targets and play roles in antibiotic lethality. Independent lines of evidence from studies of the action… 
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References

SHOWING 1-10 OF 159 REFERENCES

Antibiotics: Actions, Origins, Resistance

This new text offers a comprehensive, up to date account of those structural classes of antibiotics that have had an impact in human infectious disease. While most of the attention is on natural…

Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis.

Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

It is shown that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria's susceptibility to oxidative attack and establishing a systems-based method to tune ROS production in bacteria.

Origins and Evolution of Antibiotic Resistance

This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act.

How antibiotics kill bacteria: from targets to networks

The multilayered effects of drug–target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing are discussed.

Antibiotics induce redox-related physiological alterations as part of their lethality.

This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.

The antibiotic resistome: the nexus of chemical and genetic diversity

Understanding the molecular diversity that underlies resistance will inform the use of these drugs and guide efforts to develop new efficacious antibiotics.

Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy

  • T. LuJ. Collins
  • Biology, Engineering
    Proceedings of the National Academy of Sciences
  • 2009
It is shown that suppressing the SOS network in Escherichia coli with engineered bacteriophage enhances killing by quinolones by several orders of magnitude in vitro and significantly increases survival of infected mice in vivo.

Global Challenge of Multidrug-Resistant Acinetobacter baumannii

This review summarizes the worldwide emergence of antibiotic-resistant A. baumannii as a nosocomial pathogen and focuses on its mechanisms of resistance against selected antibiotics.

Silver Enhances Antibiotic Activity Against Gram-Negative Bacteria

This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.
...