Probing bacterial fitness in virtual chemostats

Abstract

The growth rate of a bacterial population is a fundamental quantity in microbiology, but hard to predict from mechanistic single-cell models. Simulating exponentially growing cell populations is computationally infeasible, and single-lineage estimates are biased as they do not account for phenotypic selection between cells. We present computational algorithms to efficiently estimate growth rates with arbitrary accuracy by combining ideas from branching processes and particle filtering. These can be used with general agent-based cell models at a cost quadratic in the desired accuracy, bypassing the exponential complexity of naive approaches. Applying these methods to single-cell models of Escherichia coli, we study how single-cell heterogeneity in antibiotic responses shapes population dynamics, and how bacterial locomotion and chemotaxis in fluctuating environments affect their long-term growth.