Evolutionary Dynamics of Bacterial Persistence under Nutrient/Antibiotic Actions

Diseases such as tuberculosis, chronic pneumonia, and inner ear infections are caused by bacterial biofilms. Biofilms can form on any surface such as teeth, floors, or drains. Many studies show that it is much more difficult to kill the bacteria in a biofilm than planktonic bacteria because the structure of biofilms offers additional layered protection against diffusible antimicrobials. Among the bacteria in planktonic-biofilm populations, persisters is a subpopulation that is tolerant to antibiotics and that appears to play a crucial role in survival dynamics. Understanding the dynamics of persister cells is of fundamental importance for developing effective treatments. In this research, we developed a method to better describe the behavior of persistent bacteria through specific experiments and mathematical modeling. We derived an accurate mathematical model by tightly coupling experimental data and theoretical model development. By focusing on dynamic changes in antibiotic tolerance owing to phenotypic differences between bacteria, our experiments explored specific conditions that are relevant to specifying parameters in our model. We deliver deeper intuitions to experiments that address several current hypotheses regarding phenotypic expression. By comparing our theoretical model to experimental data, we determined a parameter regime where we obtain quantitative agreement with our model. This validation supports our modeling approach and our theoretical predictions. This model can be used to enhance the development of new antibiotic treatment protocols.