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1.
Cell ; 184(21): 5405-5418.e16, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34619078

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedad de Lyme/tratamiento farmacológico , Animales , Borrelia burgdorferi/efectos de los fármacos , Calibración , Cinamatos/química , Cinamatos/farmacología , Cinamatos/uso terapéutico , Evaluación Preclínica de Medicamentos , Heces/microbiología , Femenino , Células HEK293 , Células Hep G2 , Humanos , Higromicina B/análogos & derivados , Higromicina B/química , Higromicina B/farmacología , Higromicina B/uso terapéutico , Enfermedad de Lyme/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Microbiota/efectos de los fármacos
2.
Antimicrob Agents Chemother ; 35(10): 2125-7, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1662025

RESUMEN

Hepatitis caused by mouse hepatitis virus (MHV-A59), a murine coronavirus, is accompanied by direct infection and replication of virus within the liver. We demonstrate here that the aminoglycoside hygromycin B is able to eliminate MHV-A59 infection from mouse peritoneal macrophages and cultured liver cells in vitro and is also able to reduce levels of virus replication and necrotic liver foci in vivo.


Asunto(s)
Hepatitis Viral Animal/tratamiento farmacológico , Higromicina B/uso terapéutico , Virus de la Hepatitis Murina , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Hepatitis Viral Animal/microbiología , Higromicina B/toxicidad , Hígado/microbiología , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Replicación Viral/efectos de los fármacos
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