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Cell
. 2021 Oct 14;184(21):5405-5418.e16.
doi: 10.1016/j.cell.2021.09.011. Epub 2021 Oct 6.
Nadja Leimer 1, Xiaoqian Wu 1, Yu Imai 1, Madeleine Morrissette 1, Norman Pitt 1, Quentin Favre-Godal 1, Akira Iinishi 1, Samta Jain 1, Mariaelena Caboni 1, Inga V Leus 2, Vincent Bonifay 2, Samantha Niles 1, Rachel Bargabos 1, Meghan Ghiglieri 1, Rachel Corsetti 1, Megan Krumpoch 1, Gabriel Fox 1, Sangkeun Son 1, Dorota Klepacki 3, Yury S Polikanov 4, Cecily A Freliech 5, Julie E McCarthy 5, Diane G Edmondson 6, Steven J Norris 6, Anthony D'Onofrio 1, Linden T Hu 5, Helen I Zgurskaya 2, Kim Lewis
- PMID: 34619078
- PMCID: PMC8526400 (available on 2022-10-14)
- DOI: 10.1016/j.cell.2021.09.011
Abstract
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.