A selective antibiotic for Lyme disease.
A selective antibiotic for Lyme disease.
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DOI：
10.1016/j.cell.2021.09.011
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发表时间：
2021-10-14
期刊：
影响因子：
64.5
通讯作者：
Lewis K
中科院分区：
文献类型：
--
作者：
Leimer N;Wu X;Imai Y;Morrissette M;Pitt N;Favre-Godal Q;Iinishi A;Jain S;Caboni M;Leus IV;Bonifay V;Niles S;Bargabos R;Ghiglieri M;Corsetti R;Krumpoch M;Fox G;Son S;Klepacki D;Polikanov YS;Freliech CA;McCarthy JE;Edmondson DG;Norris SJ;D'Onofrio A;Hu LT;Zgurskaya HI;Lewis K
莱姆病正在上升。它由伯氏疏螺旋体引起，仅在美国就影响了大约50万人。目前用于治疗莱姆病的抗生素是广谱的，破坏微生物组并选择非靶细菌的耐药性。因此，我们试图鉴定一种选择性作用于B的化合物。burgdorferi。对土壤微生物的筛选揭示了一种对螺旋体具有高度选择性的化合物，包括B。burgdorferi。出乎意料的是，该化合物被确定为潮霉素A，一种由吸水链霉菌产生的已知抗微生物剂。潮霉素A靶向核糖体并被B吸收。burgdorferi解释了它的选择性。潮霉素A清除了B。在小鼠中，包括在诱饵中摄入化合物的动物，对伯氏螺旋体感染的影响，并且对粪便微生物组的破坏性小于临床相关抗生素。这种选择性抗生素有望为莱姆病提供更好的治疗方法，并在环境中根除它。潮霉素A选择性地在伯氏疏螺旋体中积累，并在小鼠感染模型中根除莱姆病。使用广谱抗生素治疗特定病原体会破坏宿主微生物组，并导致抗生素耐药性。潮霉素A通过对螺旋体细菌特异性的核苷转运蛋白被选择性摄取，为螺旋体感染如莱姆病提供高度选择性的抗生素。
Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the US 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 microorganisms 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. Hygromycin A selectively accumulates in Borreliella burgdorferi and eradicates Lyme disease in a mouse model of infection The use of broad-spectrum antibiotics to treat specific pathogens can damage the host microbiome and contribute to antibiotic resistance. Hygromycin A is selectively taken up through a nucleoside transporter specific to spirochete bacteria providing a highly selective antibiotic for spirochete infections such as Lyme disease.
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影响因子：
3.7
作者：
Adrion ER;Aucott J;Lemke KW;Weiner JP
通讯作者：
Weiner JP
影响因子：
--
作者：
Gavrish E;Sit CS;Cao S;Kandror O;Spoering A;Peoples A;Ling L;Fetterman A;Hughes D;Bissell A;Torrey H;Akopian T;Mueller A;Epstein S;Goldberg A;Clardy J;Lewis K
通讯作者：
Lewis K
DOI：
10.4269/ajtmh.2011.11-0292
发表时间：
2011-12-01
影响因子：
3.3
作者：
Dolan, Marc C.;Schulze, Terry L.;Piesman, Joseph
通讯作者：
Piesman, Joseph
影响因子：
4.4
作者：
Blevins, Jon S.;Revel, Andrew T.;Norgard, Michael V.
通讯作者：
Norgard, Michael V.
影响因子：
3.1
作者：
Caimano, Melissa J.;Dunham-Ems, Star;Radolf, Justin D.
通讯作者：
Radolf, Justin D.