The BvgS PAS Domain, an Independent Sensory Perception Module in the BvgAS Phosphorelay.

To detect and respond to the diverse environments they encounter, bacteria often use two-component regulatory systems (TCS) to coordinate essential cellular processes required for survival. In pathogenic species, the BvgAS TCS regulates expression of hundreds of genes, including those encoding all known protein virulence factors, and its kinase activity is essential for respiratory infection. Maintenance of BvgS kinase activity in the lower respiratory tract (LRT) depends on the function of another TCS, PlrSR. While the periplasmic Venus flytrap domains of BvgS have been implicated in responding to so-called modulating signals (nicotinic acid and MgSO), a role for the cytoplasmic Per-Arnt-Sim (PAS) domain in signal perception has not previously been demonstrated. By comparing strains with mutations in the PAS domain-encoding region of with wild-type bacteria and , we found that although the PAS domain is not required to sense modulating signals , it is required for the inactivation of BvgS that occurs in the absence of PlrS in the LRTs of mice, suggesting that the BvgS PAS domain functions as an independent signal perception domain. Our data also indicate that the BvgS PAS domain is important for controlling absolute levels of BvgS kinase activity and the efficiency of the response to modulating signals Our results provide evidence that BvgS integrates sensory inputs from both the periplasm and the cytoplasm to control precise gene expression patterns under diverse environmental conditions. Despite high rates of vaccination, pertussis, a severe, highly contagious respiratory disease caused by the bacterium , has reemerged as a significant health threat. In and the closely related species , activity of the BvgAS two-component regulatory system is critical for colonization of the mammalian respiratory tract. We show here that the cytoplasmic PAS domain of BvgS can function as an independent signal perception domain that influences BvgS activity in response to environmental conditions. Our work is significant because it reveals a critical, yet previously unrecognized, role for the PAS domain in the BvgAS phosphorelay and provides a greater understanding of virulence regulation in .