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

Area of Science:

• Microbiology
• Bacterial Physiology
• Antibiotic Resistance

Background:

• Beta-lactam antibiotics induce distinct population-level responses in sensitive bacteria, including transient biomass increases and linear growth-killing rate correlations.
• The mechanistic link between individual bacterial cell responses and these emergent population dynamics remains poorly understood.

Purpose of the Study:

• To elucidate how collective single-cell behaviors, specifically filamentation and lysis, contribute to observed population-level biomass changes during beta-lactam antibiotic treatment.
• To establish a quantitative relationship between single-cell lysis probability and filamentation extent.

Main Methods:

• Experimental observation of bacterial filamentation and lysis dynamics under beta-lactam antibiotic stress.
• Mathematical modeling to correlate single-cell lysis probabilities with population-level biomass dynamics.
• Experimental validation of model predictions.

Main Results:

• The probability of bacterial cell lysis increases sigmoidally with the degree of filamentation.
• This sigmoidal dependence is characterized by parameters specific to bacterial strain, antibiotic concentration, and growth conditions.
• A model successfully predicted population-level biomass dynamics from single-cell lysis probabilities, which were experimentally confirmed.

Conclusions:

• The study provides a mechanistic framework connecting single-cell lysis events to population-level biomass time-kill curves.
• This framework reveals universal parameters that can describe both individual cell and population responses to beta-lactam antibiotics.
• Understanding these dynamics offers insights into bacterial population behavior under antibiotic pressure.