Like all good investors, bacteria invest in diversity to ensure survival and maximise growth. The cellular hedging strategy of “bacterial persistence” is a major contributing factor to antibiotic resistance and is responsible for the incurability of many common infections. Bacteria relegate a small proportion of their population to dormant persister cells — a rainy day fund — while the majority of the population invests in growth.
The cover image for the January 5 issue of Biophysical Journal is a graphical rendering of an experiment that probes bacterial persistence. The majority of cells, shown in blue, are actively dividing and rapidly growing the population. An extremely small proportion of the population — as few as one in a million — of the bacteria are persisters, shown graphically in red. Persisters are often overlooked due to their extreme scarcity. However, while temporarily dormant and “bunkered down,” they can revert to regular bacteria and regrow the population. Diversity in biological populations must be a key consideration behind any clinical interventions, particularly those that aim to combat antibiotic resistance. We emphasise this in the cover art through coloration and close focus on a persister in the population.
Persistence and similar hedging strategies are not just seen in bacteria, but also viruses and cancers. It is widely thought that cells’ ability to persist is an artifact of growth maximizing adaptation to the volatile, unpredictable environments in which these cells evolve. A better understanding of how biological systems adapt to uncertainty can help combat antibiotic resistance and lead to new, adaptative, therapeutic interventions. Our study provides a new theoretical foundation for studying how cells adapt to uncertainty using mathematical finance theory. The cover image, which shows an experimental study probing persistence, was inspired by new experimental opportunities enabled by our research. The computer-generated feel of the rendering emphasises the theoretical nature of our study.
The interface of experimental and theoretical science is the foundation of modern research. Our theoretical study provides a powerful platform for exploring the adaptation of biological systems to uncertainty. Perhaps bacteria are not all that different from a thrifty investor.
- Jesse Sharp, Tarunendu Mapder, Christopher Baker, Kevin Burrage, Matthew Simpson, Alexander Browning