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 2015, the CDC reported over 30,000 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 is one of three known Borrelia MTA/SAH nucleosidases (MTNs), and a key component in the methionine salvage pathway, an essential part of Borrelia burgdorferi metabolic activity. Novel BGP inhibitors were identified from in silico screening of drug databases using an E. coli MTN template. A series of subsequent compounds were synthesized based on the lead compounds, and their inhibitory activity against purified recombinant 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.

Inhibition of Borrelia burgdorferi Bgp MTA/SAH nucleosidase

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.