Abstract

Effective antibiotic use that minimizes treatment failures remains a challenge. A better understanding of how bacterial populations respond to antibiotics is necessary. Previous studies of large bacterial populations established the current deterministic framework of pharmacodynamics. Here, characterizing the dynamics of population extinction, we demonstrated the stochastic nature of eradicating bacteria with antibiotics. Antibiotics known to kill bacteria (bactericidal) induced population fluctuations. Thus, at high antibiotic concentrations, the dynamics of bacterial clearance were heterogeneous. At low concentrations, clearance still occurred with a non-zero probability. These striking outcomes of population fluctuations were well captured by our probabilistic model. Our model further suggested a strategy to facilitate eradication by increasing extinction probability. We experimentally tested this prediction for antibiotic-susceptible and clinically-isolated resistant bacteria. This new knowledge exposes fundamental limits in our ability to predict bacterial eradication. Additionally, it demonstrates the potential of using antibiotic concentrations that were previously deemed inefficacious to eradicate bacteria.

Article and author information

Author details

  1. Jessica Coates

    Microbiology and Molecular Genetics Graduate Program, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Bo Ryoung Park

    Department of Physics, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dai Le

    Department of Physics, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Emrah Şimşek

    Department of Physics, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Waqas Chaudhry

    Department of Physics, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Minsu Kim

    Microbiology and Molecular Genetics Graduate Program, Emory University, Atlanta, United States
    For correspondence
    minsu.kim@emory.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1594-4971

Funding

Research Corporation for Science Advancement (24097)

  • Jessica Coates
  • Bo Ryoung Park
  • Dai Le
  • Emrah Şimşek
  • Minsu Kim

Human Frontier Science Program (RGY0072/2015)

  • Jessica Coates
  • Bo Ryoung Park
  • Dai Le
  • Emrah Şimşek
  • Minsu Kim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Aleksandra M Walczak, Ecole Normale Superieure, France

Version history

  1. Received: October 20, 2017
  2. Accepted: February 15, 2018
  3. Accepted Manuscript published: March 6, 2018 (version 1)
  4. Version of Record published: March 12, 2018 (version 2)
  5. Version of Record updated: March 15, 2018 (version 3)

Copyright

© 2018, Coates et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jessica Coates
  2. Bo Ryoung Park
  3. Dai Le
  4. Emrah Şimşek
  5. Waqas Chaudhry
  6. Minsu Kim
(2018)
Antibiotic-induced population fluctuations and stochastic clearance of bacteria
eLife 7:e32976.
https://doi.org/10.7554/eLife.32976

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https://doi.org/10.7554/eLife.32976