Abstract
Correct decision making is fundamental for all living organisms to thrive under environmental changes. The patterns of environmental variation and the quality of available information define the most favourable strategy among multiple options, from randomly adopting a phenotypic state to sensing and reacting to environmental cues. Cellular memory-the ability to track and condition the time to switch to a different phenotypic state-can help withstand environmental fluctuations. How does memory manifest itself in unicellular organisms? We describe the population-wide consequences of phenotypic memory in microbes through a combination of deterministic modelling and stochastic simulations. Moving beyond binary switching models, our work highlights the need to consider a broader range of switching behaviours when describing microbial adaptive strategies. We show that memory in individual cells generates patterns at the population level coherent with overshoots and non-exponential lag times distributions experimentally observed in phenotypically heterogeneous populations. We emphasise the implications of our work in understanding antibiotic tolerance and, in general, bacterial survival under fluctuating environments.
Highlights
In an ideal world, living organisms would be able to adapt instantly and reliably to changing environmental conditions to maximise their instantaneous performance
Often advantageous under heterogeneous environments, this phenotypic heterogeneity is highly relevant in the studies of antibiotic resistance evolution and cancer resurgence
Numerous theoretical models exist applying a simple model of phenotypic switching
Summary
In an ideal world, living organisms would be able to adapt instantly and reliably to changing environmental conditions to maximise their instantaneous performance. Conditions may change abruptly and unpredictably, making it ineffective to mount a specific rapid response. Some responses require the synthesis of complex molecules (secretion systems or capsules in bacteria) or entering a physiological state (dormancy) that cannot be reverted instantaneously, if need be. Switching to a new phenotype may commit the cell to a response that lasts for a specific timescale different from the duration of the changing environment. Diversity in response rates can result in intricate patterns of phenotypic heterogeneity. While classical models of phenotypic heterogeneity use simple on-off switches, recent results stemming from accurate, modern experimental methods require us to delve deeper into the dynamics. We provide a first step towards a more realistic theoretical framework for phenotypic switching
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