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Volume 184, ISSUE 21, P5405-5418.e16, October 14, 2021
A selective antibiotic for Lyme disease
Nadja Leimer; Xiaoqian Wu; Yu Imai; Linden T. Hu; Helen I. Zgurskaya Kim
Published:October 06, 2021
Highlights
•
A selective screen against B. burgdorferi led to the rediscovery of hygromycin A
•
The mechanism of selectivity is puzzling because hygromycin A targets the ribosome
•
Hygromycin A is smuggled into spirochetes by the conserved transporter BmpDEFG
•
Hygromycin A is efficacious in a mouse model without disturbing the microbiome
Summary
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...
Volume 184, ISSUE 21, P5405-5418.e16, October 14, 2021
A selective antibiotic for Lyme disease
Nadja Leimer; Xiaoqian Wu; Yu Imai; Linden T. Hu; Helen I. Zgurskaya Kim
Published:October 06, 2021
Highlights
•
A selective screen against B. burgdorferi led to the rediscovery of hygromycin A
•
The mechanism of selectivity is puzzling because hygromycin A targets the ribosome
•
Hygromycin A is smuggled into spirochetes by the conserved transporter BmpDEFG
•
Hygromycin A is efficacious in a mouse model without disturbing the microbiome
Summary
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...