Stochastic response of bacterial cells to antibiotics: its mechanisms and implications for population and evolutionary dynamics

Abstract

The effectiveness of antibiotics against bacterial infections has been declining due to the emergence of resistance. Precisely understanding the response of bacteria to antibiotics is critical to maximizing antibiotic-induced bacterial eradication while minimizing the emergence of antibiotic resistance. Cell-to-cell heterogeneity in antibiotic susceptibility is observed across various bacterial species for a wide range of antibiotics. Heterogeneity in antibiotic susceptibility is not always due to the genetic differences. Rather, it can be caused by non-genetic mechanisms such as stochastic gene expression and biased partitioning upon cell division. Heterogeneous susceptibility leads to the stochastic growth and death of individual cells and stochastic fluctuations in population size. These fluctuations have important implications for the eradication of bacterial populations and the emergence of genotypic resistance.