Phenotypic delay in the evolution of bacterial antibiotic resistance: Mechanistic models and their implications

Abstract

Author summary Understanding precisely how some bacteria survive exposure to antibiotics is a major research focus. Specific mutations in the bacterial genome are known to provide protection. However, it remains unclear how much time passes between a bacterium acquiring the genetic change and being able to tolerate antibiotics—termed the phenotypic delay—and what controls this delay. Here, using computer simulations and mathematical arguments we discuss three biologically plausible mechanisms of phenotypic delay. We investigate how each mechanism would affect the outcome of laboratory experiments often used to study the evolution of antibiotic resistance, and we highlight how the delay might be detected in such experiments. We also show that the existence of the delay could explain an observed discrepancy in the measurement of mutation rates, and demonstrate that one of our models provides a superior fit to experimental data. Our work exposes how molecular details at the intracellular level can have a direct effect on evolution at the population level.

Publication
PLOS Computational Biology