Figure 2.

A model of the RpoN-RpoS σ factor cascade. During tick feeding and mammalian infection, environmental and host signals activate the RpoN-RpoS σ factor cascade. Activation of RpoN requires phosphorylation of Rrp2 and accumulation of BosR. Rrp2 is the sole prokaryotic enhancer-binding protein present in B. burgdorferi that is required for RpoN (σ⁵⁴) activation. Phosphorylation of Rrp2 not only is required for RpoN-RpoS activation, but also is indispensable for cell survival, presumably replication. Levels of BosR respond to environmental signals and accumulation of BosR activates rpoS at its RpoN-dependent promoter via an unknown mechanism. BadR represses rpoS transcription by directly binding near the RpoN-dependent promoter region. In addition to the major rpoS mRNA species transcribed from the RpoN-dependent promoter, a longer rpoS transcript is produced at low cell density from an RpoN-independent promoter located within the upstream flgJ gene. The sRNA DsrA_Bb regulates the efficiency of long rpoS mRNA species translation in response to temperature. DDB18 can regulate RpoS (σ^S) levels at the post-transcriptional level. Accumulation of rpoS transcript leads to the production of OspC, DbpA, DbpB, BBK32, and other mammalian infection-associated proteins.