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A selective antibiotic for Lyme disease.
Leimer, Nadja; Wu, Xiaoqian; Imai, Yu; Morrissette, Madeleine; Pitt, Norman; Favre-Godal, Quentin; Iinishi, Akira; Jain, Samta; Caboni, Mariaelena; Leus, Inga V; Bonifay, Vincent; Niles, Samantha; Bargabos, Rachel; Ghiglieri, Meghan; Corsetti, Rachel; Krumpoch, Megan; Fox, Gabriel; Son, Sangkeun; Klepacki, Dorota; Polikanov, Yury S; Freliech, Cecily A; McCarthy, Julie E; Edmondson, Diane G; Norris, Steven J; D'Onofrio, Anthony; Hu, Linden T; Zgurskaya, Helen I; Lewis, Kim.
Affiliation
  • Leimer N; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Wu X; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Imai Y; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Morrissette M; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Pitt N; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Favre-Godal Q; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Iinishi A; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Jain S; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Caboni M; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Leus IV; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA.
  • Bonifay V; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA.
  • Niles S; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Bargabos R; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Ghiglieri M; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Corsetti R; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Krumpoch M; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Fox G; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Son S; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Klepacki D; Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
  • Polikanov YS; Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
  • Freliech CA; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA.
  • McCarthy JE; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA.
  • Edmondson DG; Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77225, USA.
  • Norris SJ; Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77225, USA.
  • D'Onofrio A; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA.
  • Hu LT; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA 02111, USA.
  • Zgurskaya HI; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA.
  • Lewis K; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA 02115, USA. Electronic address: k.lewis@neu.edu.
Cell ; 184(21): 5405-5418.e16, 2021 10 14.
Article in En | MEDLINE | ID: mdl-34619078
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lyme Disease / Anti-Bacterial Agents Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2021 Document type: Article Affiliation country: Estados Unidos Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lyme Disease / Anti-Bacterial Agents Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2021 Document type: Article Affiliation country: Estados Unidos Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA