Title

Examination of Novel MTN inhibitors as Antibiotics to Treat Lyme Borreliosis

Document Type

Student Presentation

Presentation Date

April 2017

Faculty Sponsor

Ken Cornell

Abstract

Lyme disease is a generally treatable tick-borne zoonosis caused by Borrelia burdorferi. However, some chronic Lyme infections cause patients to experience additional symptoms for up to several months after the completion of antibiotic therapy. The discovery of novel antibiotic agents could benefit individuals who suffer from persistent infections. One promising new target for antibiotic therapy is Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTN), a key enzyme in the salvage pathway of adenine and methionine in B. burgdorferi. B. burgdorferi expresses three MTNs, termed Bgp, Pfs, and MTNN, underscoring the importance of this enzyme activity to the spirochaete. The purpose of this study was to determine the in vitro bactericidal activity of a series of benzimidazole and urea-containing novel MTN inhibitors identified by in silico screening of the NCI diversity set II database. Cultures of B. burgdorferi (N40 strain) were treated with novel MTN inhibitors for 24 hours, and the cell viability/cell death determined using both a fluorescent SYBR green/propidium iodide differential stain, and a CellTiter-Glo® luminescence assay. We found that 5 of the compounds demonstrated considerable bactericidal activity, reducing the cell viability by more than 50% at a concentration of 50μM. This constitutes grounds for further testing of these compounds.

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