Antibiotic-induced population fluctuations and stochastic clearance of bacteria

eLife

Emrah Şimşek¹  Waqas Chaudhry¹  Bo Ryoung Park¹  Dai Le¹  Jessica Coates²  Minsu Kim² 

[1] Department of Physics, Emory University, Atlanta, United States;Microbiology and Molecular Genetics Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, United States;

关键词: antibiotics;    population dynamics;    population fluctuations;    stochastic;   

DOI  :  10.7554/eLife.32976

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown