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Elife. 2018 Mar 6;7. pii: e32976. doi: 10.7554/eLife.32976.

Antibiotic-induced population fluctuations and stochastic clearance of bacteria.

Author information

1
Microbiology and Molecular Genetics Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, United States.
2
Department of Physics, Emory University, Atlanta, United States.
3
Emory Antibiotic Resistance Center, Emory University, Atlanta, United States.
#
Contributed equally

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 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.

KEYWORDS:

E. coli; antibiotics; computational biology; population dynamics; population fluctuations; stochastic; systems biology

PMID:
29508699
PMCID:
PMC5847335
DOI:
10.7554/eLife.32976
[Indexed for MEDLINE]
Free PMC Article

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