Abstract Temperate phage can initiate lysis or lysogeny after infecting a bacterial host. The genetic switch between lysis and lysogeny is mediated by phage regulatory genes as well as host and environmental factors. Recently, a new class of decision switches was identified in phage of the SPbeta group, mediated by the extracellular release of small, phage-encoded peptides termed arbitrium. Arbitrium peptides can be taken up by bacteria prior to infection, modulating the decision switch in the event of a subsequent phage infection. Increasing the concentration of arbitrium increases the chance that a phage infection will lead to lysogeny, rather than lysis. Although prior work has centered on the molecular mechanisms of arbitrium-induced switching, here we focus on how selective pressures impact the benefits of plasticity in switching responses. In this work, we examine the possible advantages of near-term adaptation of communication-based decision switches used by the SPbeta-like group. We combine a nonlinear population model with a control-theoretic approach to evaluate the relationship between a putative phage reaction norm (i.e. the probability of lysogeny as a function of arbitrium) and the extent of phage reproduction at a near-term time horizon. We measure phage reproduction in terms of a cellular-level metric previously shown to enable comparisons of near-term phage fitness across a continuum from lysis to latency. We show the adaptive potential of communication-based lysis–lysogeny responses and find that optimal switching between lysis and lysogeny increases the near-term phage reproduction compared to fixed responses, further supporting both molecular- and model-based analyses of the putative benefits of this class of decision switches. We further find that plastic responses are robust to the inclusion of cellular-level stochasticity, variation in life history traits, and variation in resource availability. These findings provide further support to explore the long-term evolution of plastic decision systems mediated by extracellular decision-signaling molecules and the feedback between phage reaction norms and ecological context.
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Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations
Ultrasensitive feedback control can improve robust gene expressions in cell populations, yet it usually requires large chemical productions that cause severe burden to cells.
Inspired by `division-of-labor' in heterogeneous populations, we propose a bistable switch circuit that utilizes quorum sensing systems to coordinate heterogeneous phenotypes' behaviors. We show that ultrasensitivity emerges from a collection of parallel bistable switches in individual cells. When applied to feedback control of population level expressions, it can achieve robust reference tracking and adaptation to disturbances. In particular, we demonstrate that molecular sequestration enables tunable hysteresis in single switches, leading to a wide range of stable population level expressions.
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- Award ID(s):
- 2020039
- NSF-PAR ID:
- 10274112
- Date Published:
- Journal Name:
- Proceedings of the American Control Conference
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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