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Title: Insights into the complex regulation of rpoS in Borrelia burgodorferi

item Frye, Jonathan

Submitted to: Molecular Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2007
Publication Date: 7/10/2007
Citation: Burtnick, M.N., Downey, J., Brett, P.J., Boylan, J.A., Frye, J.G., Hoover, T.R., Gherardini, F.C. 2007. Insights into the complex regulation of rpoS in Borrelia burgodorferi. Molecular Microbiology. 65(2):277-293.

Interpretive Summary: Lyme disease is the most prevalent tick transmitted disease in the US and is caused by the spirochete, Borrelia burgdorferi. This bacterium is transmitted to the human host while the tick takes a blood meal. Little is understood about how this bacterium changes its gene expression during the establishment of an infection in a new host. To investigate this we have performed genetic studies on the regulatory genes found in this bacterium. These studies found that sigma54 dependent gene expression is necessary during the infection process. In most bacteria, a histidine kinase (Hk2) detects a signal, and passes that signal to a response regulator protein (Rrp2) which then activates gene expression by sigma54. We found that a B. burgdoferi strain lacking the histidine kinase, Hk2, still expresses sigma54 dependent genes. This is a unique regulatory network used by B. burgdorferi to survive in diverse hosts and cause disease in humans.

Technical Abstract: The coordinated regulation of gene expression is required for the transmission and survival of Borrelia burgdorferi in different hosts, and the sigma factor RpoS (sigmaS), as regulated by RpoN (sigma54), has been shown to regulate key proteins in these processes. We show that rpoS has one sigma54-dependent and an additional sigma54-independent promoter. The sigma54-dependent activation of sigmaS requires response regulator, Rrp2 (BB0763). Purified recombinant Rrp2 did not bind to the DNA upstream of rpoS in gel-shift assays, nor did Rrp2ÿ123, a truncated constitutively active form of Rrp2. Interestingly, Rrp2ÿ123 activation of a rpoS-lacZ reporter gene in E. coli was sigma54-dependent but did not require DNA sequences upstream of the rpoS-P/O. Similarly, QRT-PCR experiments on reporter cat constructs in B. burgdorferi indicated that DNA sequences upstream of the sigma54-dependent rpoS promoter were not needed by Rrp2 to activate transcription of rpoS. Further experiments showed that rpoN is required for stationary phase expression of rpoS in B. burgdorferi, but that the histidine kinase Hk2 is not absolutely essential. This suggested that another histidine kinase or small molecular weight phosphate donors could activate Rrp2, providing multiple signaling pathways for modulating expression of the sigma54/sigmaS regulon in B. burgdorferi.