Mechanism of repression of the glycerol utilization operon in Borrelia burgdorferi

Lyme disease pathogen Borrelia burgdorferi, switches carbohydrate utilization while transmitting between two disparate hosts, an Ixodes tick vector and a mammalian host. The ability to use glycerol is important for B. burgdorferi to colonize and persist in the tick vector, and expression of the glpFKD (glp) operon for glycerol uptake/utilization is tightly regulated during the enzootic cycle of B. burgdorferi between ticks and mammals. In present study, we identified a cis element within the 5 untranslated region of glp that negatively regulates the glp expression. This repression of glp is independent of RpoS. We further show that BadR directly binds to this cis element and represses glp. The efficiency of BadR binding in the presence of c-di-GMP and various carbohydrates were also assessed. This finding, along with previous findings of positive regulation of glp expression by the c-di-GMP signaling pathway and negative regulation by the alternative sigma factor RpoS, demonstrates that B. burgdorferi employs multi-layer regulatory mechanisms to coordinate glp expression during its enzootic cycle.