The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorfen

In nature, the Lyme disease spirochete Borrelia burgdorfeh cycles between the unrelated environments of the lxodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorfeh must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorfeh to the tick environment. B. burgdorfeh possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding Pi1Z-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorfeh have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorfeh may lead to the identification of mechanisms that are critical for the survival of B. burgdorfeh in the tick phase of the enzootic cycle as well as potentially delineate a role Of any) c-di-GMP may play in the transmission and virulence of B. burgdorfeh during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.