Identification of inhibitors of BB323 and BB238 interaction in Borrelia burgdorferi (chronic Lyme disease)

National Center For Advancing Translational Sciences

Investigators

Abstract

The goal of this collaboration is to follow up on recent discoveries to exploit a critical protein-protein interaction (PPI) in B. burgdorferi that is critical for the infectivity of Lyme disease agents and identify small molecule inhibitors of this interaction. During the reporting period, the collaborative team developed and miniaturized an AlphaLISA-based PPI assay to 1536-well format, and primary screening of libraries has commenced. Hit confirmation is underway using the primary assay, as well as counterscreen assays using the TruHits assay and a GST-HIS target using the primary assay to filter out false negatives. An MST biophysical approach for testing direct binding of compounds to proteins, as well as perturbation of the PPI using a competition assay method, are being developed to further characterize hits. Hits are additionally being characterized in an orthogonal approach, measuring perturbation of the 238-323 interaction in intact Borrelia and mouse models of Borrelia burgdorferi infection.