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Antimicrobial-Mediated Bacterial Suicide

  • Yuzhi Hong
  • Karl Drlica
  • Xilin Zhao
Chapter
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

Abstract

One way to restrict the emergence of new antibiotic resistance is to make antimicrobials more lethal. To achieve that, a better understanding of how antimicrobials kill pathogens is needed. In the last decade, the idea emerged that reactive oxygen species (ROS) play a role in the lethal action of diverse antimicrobials. Experimental support was obtained (1) by measuring the effects of antimicrobials on intracellular ROS accumulation using dyes that become fluorescent in the presence of ROS and (2) by altering antimicrobial lethality using mutations in genes known to protect from oxidative damage and by using chemicals expected to alter ROS levels. Moreover, an ROS-mediated death process, which is blocked by treatment with an ROS-mitigating agent, continues after removal of the original lethal stress that triggers the ROS cascade. Challenges to the idea that ROS contribute to antimicrobial lethality led to refinements and additional support. For example, a drop in ROS explains the paradoxical loss of killing seen at very high concentrations of quinolone antibacterials, and an increase in ROS accounts for most of thymineless death. A potential consequence of ROS-mediated antimicrobial action is reduced antimicrobial effectiveness when antioxidants are consumed as nutritional supplements during antimicrobial therapy. Another is novel cross-tolerance that has not been previously considered with combination therapies. Overall, the experimental observations fit well with the concept that bacteria respond to severe stress by building up ROS levels and self-destructing.

Notes

Acknowledgments

We thank the following for critical comments on the manuscript: Marila Gennaro and Bo Shopsin.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health SciencesNewarkUSA
  2. 2.Department of MicrobiologyBiochemistry, & Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health SciencesNewarkUSA
  3. 3.State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen UniversityXiamenChina

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