Bistable switch-like behavior is a ubiquitous feature of gene regulatory networks with decision-making capabilities. Type II toxin-antitoxin (TA) systems are hypothesized to facilitate a bistable switch in toxin concentration that influences the dormancy transition in persister cells. However, a series of recent retractions has raised fundamental questions concerning the exact mechanism of toxin propagation in persister cells and the relationship between type II TA systems and cellular dormancy. Through a careful modeling search, we identify how sp: bistablilty can emerge in type II TA systems by systematically modifying a basic model for the RelBE system with other common biological mechanisms. Our systematic search uncovers a new combination of mechanisms influencing bistability in type II TA systems and explores how toxin bistability emerges through synergistic interactions between paired type II TA systems. Our analysis also illustrates how Descartes’ rule of signs and the resultant can be used as a powerful delineator of bistability in mathematical systems regardless of application.

双稳态开关样行为是具有决策能力的基因调控网络的普遍特征。假设 II 型毒素-抗毒素 (TA) 系统促进毒素浓度的双稳态转换，从而影响持久细胞的休眠转变。然而，最近的一系列撤回提出了关于毒素在持久细胞中传播的确切机制以及 II 型 TA 系统与细胞休眠之间的关系的基本问题。通过仔细的建模搜索，我们通过系统地修改具有其他常见生物机制的 RelBE 系统的基本模型，确定了 sp: 双稳态如何出现在 II 型 TA 系统中。我们的系统搜索揭示了影响 II 型 TA 系统双稳定性的机制的新组合，并探索了如何通过成对的 II 型 TA 系统之间的协同相互作用出现毒素双稳定性。我们的分析还说明了笛卡尔的符号规则及其结果如何在数学系统中用作强大的双稳态描述器，而不管应用如何。