Phenotypic-dependent variability and the emergence of tolerance in bacterial populations

TL;DR

This paper investigates how bacterial populations rapidly evolve tolerance to antibiotics through phenotypic lag time variability, combining experimental evidence with a new individual-based model and a generalized mathematical framework.

Contribution

It introduces a parsimonious individual-based model capturing phenotypic lag time evolution and develops a generalized mathematical framework extending population genetics equations.

Findings

Model reproduces empirical lag time distributions

Distribution develops heavy tails with large lag individuals

Framework accurately describes stochastic phenotypic evolution

Abstract

Ecological and evolutionary dynamics have been historically regarded as unfolding at broadly separated timescales. However, these two types of processes are nowadays well documented to much more tightly than traditionally assumed, especially in communities of microorganisms. With this motivation in mind, here we scrutinize recent experimental results showing evidence of rapid evolution of tolerance by lag in bacterial populations that are periodically exposed to antibiotic stress in laboratory conditions. In particular, the distribution of single-cell lag times evolves its average value to approximately fit the antibiotic-exposure time. Moreover, the distribution develops right skewed heavy tails, revealing the presence of individuals with anomalously large lag times. Here, we develop a parsimonious individual-based model mimicking the actual demographic processes of the experimental setup. Individuals are characterized by a single phenotypic trait: their intrinsic lag time, which is transmitted with variation to the progeny. The model (in a version in which the amplitude of phenotypic variations grows with the parent\'s lag time) is able to reproduce quite well the key empirical observations. Furthermore, we develop a general mathematical framework allowing us to describe with good accuracy the properties of the stochastic model by means of a macroscopic equation, which generalizes the Crow Kimura equation in population genetics. From a broader perspective, this work represents a benchmark for the mathematical framework designed to tackle much more general eco-evolutionary problems, thus paving the road to further research avenues.