Continuous control of flagellar gene expression by the σ²⁸-FlgM regulatory circuit in Salmonella enterica

The flagellar genes in Salmonella enterica are expressed in a temporal hierarchy that mirrors the assembly process itself. The σ²⁸-FlgM regulatory circuit plays a key role in controlling this temporal hierarchy. This circuit ensures that the class 3 genes are expressed only when the hook-basal body (HBB), a key intermediate in flagellar assembly, is complete. In this work, we investigated the role of the σ²⁸-FlgM regulatory circuit in controlling the timing and magnitude of class 3 gene expression using a combination of mathematical modelling and experimental analysis. Analysis of the model predicted that this circuit continuously controls class 3 gene expression in response to HBB abundance. We experimentally validated these predictions by eliminating different components of the σ²⁸-FlgM regulatory system and also by rewiring the transcriptional hierarchy. Based on these results, we conclude that the σ²⁸-FlgM regulatory circuit continuously senses the HBB assembly process and regulates class 3 gene expression and possibly flagellar numbers in response.