Lyme disease is a tick-transmitted illness caused by the spirochaete Borrelia burgdorferi. If left untreated, Lyme disease can lead to serious health problems such as paralysis, muscle weakness, and inflammation of the joints. In 2014, the CDC reported over 25,000 confirmed cases of Lyme disease in the U.S. Although there are existing antibiotics for Lyme disease; such as doxycycline, amoxicillin and cefuroxime axetil; some patients display intolerance to these treatments. Here we report the development of alternative drugs that target Borrelia Glycosaminoglycan-binding Protein (BGP). BGP has shown MTA/SAH nucleosidase activity, a key component in the methionine salvage pathway and an essential part of Borrelia burgdorferi metabolic activity. Novel BGP inhibitors were identified from in silico screening of drug databases. A series of subsequent compounds were synthesized based on the lead compounds, and there inhibitory activity against BGP assessed using spectrophotometric enzyme assays. Several of the compounds show promising anti-BGP activity and in vitro antibiotic activity against Borrelia cultures. This work provides the basis for further development of these drugs as novel Lyme disease treatments.

Analysis of novel inhibitors of Borrelia burgdorferi BGP protein: Potential new antibiotics to treat lyme disease

253rd National Meeting (2017)

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