Preliminary studies conducted at the collaborating institution, Missouri State University (USA), have demonstrated that one of the existing local anesthetics markedly enhances antimicrobial activity against mycobacteria. In this project, Japan and the United States will jointly pursue elucidation of the molecular mechanisms underlying this synergistic effect (U.S. side) and validation of its efficacy using clinical isolates of Mycobacterium avium complex (MAC) (Japan side). In addition, whole-genome sequencing will be performed in cases where resistant strains emerge, in order to clarify the mechanisms of resistance.This study adopts a drug repositioning approach, applying existing drugs to new therapeutic purposes, and has the potential to provide a novel breakthrough in this disease area, where the development of new therapeutic agents has been particularly challenging.
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