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.

A quantitative approach to easily characterize and predict cell death and escape to β-lactam treatments

“…It is known that for a given β-lactam concentration, the time to cell lysis is inversely proportional to the growth rate 9,10 . Because the elongation rate is not significantly affected by the antibiotic, this suggests that the death mechanism can be modelled with a critical cell length, reachable when cell septation is blocked 11 . Cell filaments longer than this threshold experience a significant death rate.…”

“…The model is not fitted to actual data. Going further, Kim and colleagues characterized the death probability as a function of the cell length using videomicroscopy data 11 . A model is used semi-quantitatively to predict the temporal evolution of the live biomass for susceptible cells.…”