Working model of PlzA connecting the two signaling systems in B. burgdorferi, Hk1-Rrp1 and Hk2-Rrp2. The product of the Hk1-Rrp1 signaling system, c-di-GMP, binds to the effector PlzA and positively regulates the BosR protein level. PlzA also regulates the bosR mRNA level independently of c-di-GMP. An elevated BosR level increases the transcription of rpoS from an RpoN (σ54)-type promoter whose activation is governed by RpoN and phosphorylated Rrp2 by Hk2 or acetyl phosphate (AcP). RpoS, in turn, controls expression of many genes, such as ospC (essential for mammalian infection) and chbC (important to tick colonization). For simplicity, other functions of Rrp1 and PlzA, such as motility and glycerol utilization, as well as other factors involved in RpoS regulation, are not included in the model.