Antibiotic-induced population fluctuations and stochastic clearance of bacteria
- Emory University, United States
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.
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Author details
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.
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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Antibiotic-induced population fluctuations and stochastic clearance of bacteria
eLife 7:e32976.
https://doi.org/10.7554/eLife.32976
