A deformylase inhibitor expands therapeutic options for Lyme disease
Lyme disease is surging. This vector-borne infection imposes a substantial public health burden. Broad-spectrum doxycycline and ceftriaxone disrupt the gut microbiome, drive resistance in commensals, and offer suboptimal efficacy against neuroborreliosis. Here we report that forazemin (formerly BB-83698), an orally bioavailable peptide deformylase inhibitor exhibits potent, selective bactericidal activity against spirochaetes including diverse Borrelia species. Targeting the deformylation of nascent peptides, forazemin halted protein synthesis, thereby killing the spirochaetes. In murine Lyme borreliosis and neuroborreliosis models, short oral dosing regimens rapidly cleared infection, and outperform doxycycline in tick-bite prophylaxis. Forazemin preserved microbiome diversity and spared beneficial gut symbionts. Forazemin's profile positions it as a promising candidate for both treatment and prevention of Lyme disease.