Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen.

In , the Lyme disease pathogen, differential gene expression is primarily controlled by the alternative sigma factor RpoS (σ). Understanding how RpoS levels are regulated is crucial for elucidating how is maintained throughout its enzootic cycle. Our recent studies have shown that a homolog of Fur/PerR repressor/activator, BosR, functions as an RNA-binding protein that controls the mRNA stability. However, the mechanisms of regulation of BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we revealed a positive feedback loop between RpoS and BosR, where RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of significantly reduced BosR levels, while artificial induction of resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect mRNA levels but instead modulates the turnover rate of the BosR protein. Furthermore, we demonstrated that environmental cues do not directly influence expression but instead induce transcription and RpoS production, thereby enhancing BosR protein levels. This discovery adds a new layer of complexity to the RpoN-RpoS pathway and suggests the need to re-evaluate the factors and signals previously believed to regulate RpoS levels through BosR.