Hygromycin A treatment of Borrelia burgdorferi-infected Peromyscus leucopus suggests potential as a reservoir-targeted antibiotic

Stephanie S You; Muskan Shrestha; Jeffrey S Bourgeois; Luke H Clendenen; Nadja Leimer; Kim Lewis; Sam R Telford; Linden T Hu

doi:10.1093/infdis/jiaf363

Hygromycin A treatment of Borrelia burgdorferi-infected Peromyscus leucopus suggests potential as a reservoir-targeted antibiotic

J Infect Dis. 2025 Jul 4:jiaf363. doi: 10.1093/infdis/jiaf363. Online ahead of print.

Authors

Stephanie S You^{1

2}, Muskan Shrestha^{1

2}, Jeffrey S Bourgeois^{1

2}, Luke H Clendenen^{1

2}, Nadja Leimer³, Kim Lewis³, Sam R Telford^{1

4}, Linden T Hu^{1

2}

Affiliations

¹ Tufts Lyme Disease Initiative, Tufts University School of Medicine, Boston, MA, 02111, United States of America.
² Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, 02111, United States of America.
³ Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, 02115, United States of America.
⁴ Department of Infectious Disease and Global Health, Tufts University, North Grafton, MA, 01536, United States of America.

PMID: 40614169
DOI: 10.1093/infdis/jiaf363

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 B. 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 U.S. 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.

Keywords: Borrelia burgdorferi; Borreliella burgdorferi; Antibiotics; Hygromycin A; Lyme disease; Reservoir.

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