A selective antibiotic for Lyme disease

Cell. 2021 Oct 14;184(21):5405-5418.e16. doi: 10.1016/j.cell.2021.09.011. Epub 2021 Oct 6.


Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.

Keywords: B. burgdorferi; Lyme disease; Spirochetes; antibiotic; microbiome; transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Borrelia burgdorferi / drug effects
  • Calibration
  • Cinnamates / chemistry
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use
  • Drug Evaluation, Preclinical
  • Feces / microbiology
  • Female
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Hygromycin B / analogs & derivatives
  • Hygromycin B / chemistry
  • Hygromycin B / pharmacology
  • Hygromycin B / therapeutic use
  • Lyme Disease / drug therapy*
  • Lyme Disease / microbiology
  • Mice
  • Microbial Sensitivity Tests
  • Microbiota / drug effects


  • Anti-Bacterial Agents
  • Cinnamates
  • Hygromycin B
  • hygromycin A