5’-Methylthioadenosine/ S-Adenosylhomocysteine Nucleosidases as a Target for Antibiotics in Borrelia burgdorferi

Lyme disease is caused by the bacterial spirochaete Borrelia burgdorferi acquired through the bite of infected ticks. Lyme disease symptoms includes fever, fatigue, and erythema migrans skin rash. If untreated, the bacteria can spread to the joints, heart, and nervous system to form a multisystem disease. While most patients recover with antibiotics, some develop chronic Lyme disease making the discovery of new therapeutics imperative. In this study, 5'-methylthio-adenosine/S-adenosylhomocysteine nucleosidase (MTN) was explored as a drug target for B. burgdorferi . C ompounds with the potential to bind enzyme active sites and inhibit activity were screened against recombinant Borrelia MTNs, and their Ki and IC ₅₀ s assessed to determine antispirochaete activity. MTN inhibitors show potent nanomolar K _i values and micromolar in vitro antibiotic activities. On the basis of this analysis, structure-based inhibitors can be developed as highly effective novel antibiotic therapies against B. burgdorferi for the treatment of Lyme disease.