. The Borrelia burgdorferi infectious cycle requires the organism to survive in both tick and mammalian hosts. Previous studies have shown that B. burgdorferi accomplishes the adjustment to the vast differences in environmental challenges presented by these hosts in part by regulating expression of its surface proteins. In our preliminary studies, we have identified the first host molecule, the adrenergic hormone norepinephrine (NE), which is recognized by B. burgdorferi as a signal for a specific environmental change. NE binds specifically to B. burgdorferi. The presence of NE increases production of outer surface protein A (OspA) of B. burgdorferi, a protein critical in tick colonization. Up-regulation of OspA in the presence of NE can be blocked by the use of competitive inhibitors such as propranolol. We have also been able to show that propranolol inhibits OspA expression in an in vivo model. B. burgdorferi from ticks that were fed on infected mice treated with propranolol expressed less OspA than those fed on mice administered sham. In addition, the ticks fed on propranolol treated mice acquired B. burgdorferi at significantly lower rates than those fed on mice treated with sham suggesting that recognition of NE plays an important role in the infectious cycle of B. burgdorferi. We hypothesize that the organism may co-opt host adrenergic signals to inform of local changes that predict the presence of a tick host and allow it to prepare for transition to a new environment. In this proposal, we describe our plans to understand how the recognition of host catecholamines affects bacterial processes. To better understand the proteins that are required for movement from a mouse to tick host, we will first identify genes that are co-regulated with OspA in response to NE by gene array and two dimensional protein electrophoresis. We will identify the B. burgdorferi receptor for catecholamines using techniques such as crosslinking of radioactive NE, liquid chromatography and/or immunoprecipitation. A better understanding of how B. burgdorferi has learned to intercept host hormonal cell to cell communication and utilize it for its own purposes could lead to new strategies for controlling infection in ticks which would have a direct impact on disease transmission to humans. The mechanisms by which B. burgdorferi recognizes its environment and prepares for transition from a mouse to a tick host have been poorly understood. The identification of host hormones as signaling molecules important in this process offers important insight into how the organism may accomplish its adaptations to its different hosts. Understanding the elements that are critical to host adaptation may lead to new strategies for disrupting the ability of the organism to survive in its natural hosts, thus reducing transmission to humans.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Host Interactions with Bacterial Pathogens Study Section (HIBP)
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Breen, Joseph J
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Tufts University
United States
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Troy, Erin B; Lin, Tao; Gao, Lihui et al. (2013) Understanding barriers to Borrelia burgdorferi dissemination during infection using massively parallel sequencing. Infect Immun 81:2347-57
Petnicki-Ocwieja, Tanja; Chung, Erin; Acosta, David I et al. (2013) TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi. Infect Immun 81:402-10
Radolf, Justin D; Caimano, Melissa J; Stevenson, Brian et al. (2012) Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol 10:87-99
Petnicki-Ocwieja, Tanja; DeFrancesco, Alicia S; Chung, Erin et al. (2011) Nod2 suppresses Borrelia burgdorferi mediated murine Lyme arthritis and carditis through the induction of tolerance. PLoS One 6:e17414