Mapping single-cell responses to population-level dynamics during antibiotic treatment

Abstract

Treatment of sensitive bacteria with beta-lactam antibiotics often leads to two salient population-level features: a transient increase in total population biomass before a subsequent decline, and a linear correlation between growth and killing rates. However, it remains unclear how these population-level responses emerge from collective single-cell responses. During beta-lactam treatment, it is well recognized that individual cells often exhibit varying degrees of filamentation before lysis. We show that the probability of cell lysis increases with the extent of filamentation and that this dependence is characterized by unique parameters that are specific to bacterial strain, antibiotic dose, and growth condition. Modeling demonstrates how the single-cell lysis probabilities can give rise to population-level biomass dynamics, which were experimentally validated. This mapping provides insights into how the population biomass time-kill curve emerges from single cells and allows the representation of both single-and population-level responses with universal parameters.