Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance

Area of Science:

• Evolutionary biology
• Microbiology
• Genetics

Background:

• Epigenetic inheritance involves transmitting non-genetic material, influencing offspring traits.
• Bacteria exhibit extensive epigenetic inheritance, with many components passed to progeny.
• Bacterial persister cells show antibiotic resistance, often viewed as bet-hedging, not epigenetic inheritance.

Purpose of the Study:

• To model bacterial persister cell formation through epigenetic inheritance.
• To re-interpret empirical findings on antibiotic tolerance within an epigenetic framework.
• To highlight phenotypic drug tolerance as a key example of epigenetic inheritance in evolution.

Main Methods:

• Development of a simplified mathematical model.
• Analysis of existing empirical data on bacterial persister cells.
• Integration of cellular noise into epigenetic inheritance models.

Main Results:

• Empirical findings on bacterial antibiotic tolerance are explained by epigenetic inheritance and cellular noise.
• A model combining epigenetic inheritance and noise provides a simpler explanation for persister cell phenotypes.
• This approach offers an alternative to the bet-hedging strategy explanation.

Conclusions:

• Phenotypic drug tolerance in bacteria is likely driven by epigenetic inheritance.
• Epigenetic inheritance provides a unifying framework for understanding bacterial persister cells.
• Bacteria offer a model system for studying evolution under epigenetic inheritance.