Abstract
Lyme disease spirochetes are maintained in natural reservoirs before spilling over into human populations. Targeting these reservoirs with vaccinations or antibiotics could impact the Borrelia burgdorferi enzootic cycle and reduce the risk of human Lyme disease. In this work we report that the narrow-spectrum antibiotic hygromycin A is sufficient to disrupt B burgdorferi transmission from the main eastern US reservoir, Peromyscus leucopus, to ticks. Additionally, hygromycin A-containing baits can clear B burgdorferi from P leucopus. These studies lay the foundation for the use of hygromycin A as a reservoir-targeted antibiotic to eradicate B burgdorferi in the wild.