Robust, linear correlations between growth rates and β-lactam-mediated lysis rates

Area of Science:

• Microbiology
• Pharmacology
• Mathematical Biology

Background:

• Faster bacterial growth correlates with faster killing by beta-lactam antibiotics.
• Bacterial persistence describes dormant cells tolerant to antibiotics, a concept often used in modeling.
• Quantification of growth rate's predictive power on lysis rate under diverse conditions is lacking.

Purpose of the Study:

• To quantify the relationship between bacterial growth rate and lysis rate upon beta-lactam antibiotic treatment.
• To determine if bacterial growth rate can predict lysis rate across various conditions, species, and strains.
• To provide a quantitative foundation for antibiotic therapy and population dynamics modeling.

Main Methods:

• Experimental automation was used to measure over 1,000 growth and killing curves.
• Experiments involved eight combinations of antibiotics, bacterial species, and strains, including clinical isolates.
• Mathematical modeling was employed to explain population-level observations through single-cell responses.

Main Results:

• Bacterial population lysis rate shows a linear dependence on the instantaneous growth rate, irrespective of modulation method.
• This linear relationship holds true across different bacterium-antibiotic pairs and conditions.
• Single-cell responses to antibiotic treatment explain the observed population-level dynamics.

Conclusions:

• Bacterial growth rate is a robust predictor of lysis rate under beta-lactam antibiotic exposure.
• The linear growth-lysis rate relationship serves as a dynamic signature for bacterium-antibiotic interactions.
• This finding supports the design of combination antibiotic therapies and prediction of population structure changes.